REFERENCES
1. Goodman LS, Wintrobe MM, Dameshek W, et al. Nitrogen mustard therapy; use of methyl-bis (beta-chloroethyl) amine hydrochloride and tris (beta-chloroethyl) amine hydrochloride for Hodgkin’s disease, lymphosarcoma, leukemia and certain allied and miscellaneous disorders. JAMA 1946;132:126-32.
2. Farber S, Diamond LK. Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroyl-glutamic acid. N Engl J Med 1948;238:787-93.
3. Burchenal JH, Holmberg EA. The utility of resistant leukemias in screening for chemotherapeutic activity. Ann N Y Acad Sci 1958;76:826-31; discussion 832.
4. Danø K. Active outward transport of daunomycin in resistant Ehrlich ascites tumor cells. Biochimica et Biophysica Acta (BBA) - Biomembranes 1973;323:466-83.
5. Chen YN, Mickley LA, Schwartz AM, et al. Characterization of adriamycin-resistant human breast cancer cells which display overexpression of a novel resistance-related membrane protein. J Biol Chem 1990;265:10073-80.
6. Cole SP, Bhardwaj G, Gerlach JH, et al. Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science 1992;258:1650-4.
7. Doyle LA, Yang W, Abruzzo LV, et al. A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc Natl Acad Sci U S A 1998;95:15665-70.
8. Marusyk A, Polyak K. Tumor heterogeneity: causes and consequences. Biochim Biophys Acta 2010;1805:105-17.
10. Gillet JP, Gottesman MM. Mechanisms of multidrug resistance in cancer. Methods Mol Biol 2010;596:47-76.
11. Rascio F, Spadaccino F, Rocchetti MT, et al. The pathogenic role of PI3K/AKT pathway in cancer onset and drug resistance: an updated review. Cancers (Basel) 2021;13:3949.
12. Mansoori B, Mohammadi A, Davudian S, Shirjang S, Baradaran B. The different mechanisms of cancer drug resistance: a brief review. Adv Pharm Bull 2017;7:339-48.
13. Jayaraj R, Nayagam SG, Kar A, et al. Clinical theragnostic relationship between drug-resistance specific miRNA expressions, chemotherapeutic resistance, and sensitivity in breast cancer: a systematic review and meta-analysis. Cells 2019;8:1250.
14. Ruan T, Liu W, Tao K, Wu C. A Review of research progress in multidrug-resistance mechanisms in gastric cancer. Onco Targets Ther 2020;13:1797-807.
15. Aleksakhina SN, Kashyap A, Imyanitov EN. Mechanisms of acquired tumor drug resistance. Biochim Biophys Acta Rev Cancer 2019;1872:188310.
17. . Warburg, O. H. The metabolism of tumours: investigations from the Kaiser Wilhelm Institute for Biology; Berlin-Dahlem: Constable & Company Limited; 1930.
18. Reshkin SJ, Bellizzi A, Caldeira S, et al. Na+/H+ exchanger-dependent intracellular alkalinization is an early event in malignant transformation and plays an essential role in the development of subsequent transformation-associated phenotypes. FASEB J 2000;14:2185-97.
19. Hussain SA, Ganesan R, Reynolds G, et al. Hypoxia-regulated carbonic anhydrase IX expression is associated with poor survival in patients with invasive breast cancer. Br J Cancer 2007;96:104-9.
20. Benej M, Pastorekova S, Pastorek J. Carbonic anhydrase IX: regulation and role in cancer. Subcell Biochem 2014;75:199-219.
21. Luong-Player A, Liu H, Wang HL, Lin F. Immunohistochemical reevaluation of carbonic anhydrase IX (CA IX) expression in tumors and normal tissues. Am J Clin Pathol 2014;141:219-25.
22. Schmidt J, Oppermann E, Blaheta RA, et al. Carbonic-anhydrase IX expression is increased in thyroid cancer tissue and represents a potential therapeutic target to eradicate thyroid tumor-initiating cells. Mol Cell Endocrinol 2021;535:111382.
23. Kaluz S, Kaluzová M, Liao SY, Lerman M, Stanbridge EJ. Transcriptional control of the tumor- and hypoxia-marker carbonic anhydrase 9: a one transcription factor (HIF-1) show? Biochim Biophys Acta 2009;1795:162-72.
24. Koukourakis MI, Bentzen SM, Giatromanolaki A, et al. Endogenous markers of two separate hypoxia response pathways (hypoxia inducible factor 2 alpha and carbonic anhydrase 9) are associated with radiotherapy failure in head and neck cancer patients recruited in the CHART randomized trial. J Clin Oncol 2006;24:727-35.
25. Olive PL, Aquino-Parsons C, MacPhail SH, et al. Carbonic anhydrase 9 as an endogenous marker for hypoxic cells in cervical cancer. Cancer Res 2001;61:8924-9.
26. Chia SK, Wykoff CC, Watson PH, et al. Prognostic significance of a novel hypoxia-regulated marker, carbonic anhydrase IX, in invasive breast carcinoma. J Clin Oncol 2001;19:3660-8.
27. Yoo H, Baia GS, Smith JS, et al. Expression of the hypoxia marker carbonic anhydrase 9 is associated with anaplastic phenotypes in meningiomas. Clin Cancer Res 2007;13:68-75.
28. Pastorekova S, Gillies RJ. The role of carbonic anhydrase IX in cancer development: links to hypoxia, acidosis, and beyond. Cancer Metastasis Rev 2019;38:65-77.
29. Pastorekova S, Ratcliffe PJ, Pastorek J. Molecular mechanisms of carbonic anhydrase IX-mediated pH regulation under hypoxia. BJU Int 2008;101 Suppl 4:8-15.
30. Newell K, Franchi A, Pouysségur J, Tannock I. Studies with glycolysis-deficient cells suggest that production of lactic acid is not the only cause of tumor acidity. Proc Natl Acad Sci ;90:1127-31.
31. Pinheiro C, Albergaria A, Paredes J, et al. Monocarboxylate transporter 1 is up-regulated in basal-like breast carcinoma. Histopathology 2010;56:860-7.
32. Pértega-Gomes N, Vizcaíno JR, Miranda-Gonçalves V, et al. Monocarboxylate transporter 4 (MCT4) and CD147 overexpression is associated with poor prognosis in prostate cancer. BMC Cancer 2011;11:312.
33. Pinheiro C, Longatto-Filho A, Azevedo-Silva J, Casal M, Schmitt FC, Baltazar F. Role of monocarboxylate transporters in human cancers: state of the art. J Bioenerg Biomembr 2012;44:127-39.
34. Puri S, Juvale K. Monocarboxylate transporter 1 and 4 inhibitors as potential therapeutics for treating solid tumours: a review with structure-activity relationship insights. Eur J Med Chem 2020;199:112393.
35. Yoshida GJ. The Harmonious interplay of amino acid and Monocarboxylate transporters induces the robustness of cancer cells. Metabolites 2021;11:27.
36. Payen VL, Mina E, Van Hée VF, Porporato PE, Sonveaux P. Monocarboxylate transporters in cancer. Mol Metab 2020;33:48-66.
37. Sun X, Wang M, Wang M, et al. Role of proton-coupled Monocarboxylate transporters in cancer: from metabolic crosstalk to therapeutic potential. Front Cell Dev Biol 2020;8:651.
38. Baltazar F, Pinheiro C, Morais-Santos F, et al. Monocarboxylate transporters as targets and mediators in cancer therapy response. Histol Histopathol 2014;29:1511-24. Available from:
39. Hao J, Chen H, Madigan MC, et al. Co-expression of CD147 (EMMPRIN), CD44v3-10, MDR1 and monocarboxylate transporters is associated with prostate cancer drug resistance and progression. Br J Cancer 2010;103:1008-18.
41. Mahoney BP, Raghunand N, Baggett B, Gillies RJ. Tumor acidity, ion trapping and chemotherapeutics. I. Acid pH affects the distribution of chemotherapeutic agents in vitro. Biochem Pharmacol 2003;66:1207-18.
42. Raghunand N, Altbach MI, van Sluis R, et al. Plasmalemmal pH-gradients in drug-sensitive and drug-resistant MCF-7 human breast carcinoma xenografts measured by 31P magnetic resonance spectroscopy. Biochem Pharmacol 1999;57:309-12.
43. Raghunand N, Mahoney BP, Gillies RJ. Tumor acidity, ion trapping and chemotherapeutics. Biochem Pharmacol 2003;66:1219-29.
44. Gu Y, Zhao Z, Niu G, et al. Visualizing semipermeability of the cell membrane using a pH-responsive ratiometric AIEgen. Chem Sci 2020;11:5753-8.
45. Milito A, Fais S. Proton pump inhibitors may reduce tumour resistance. Expert Opin Pharmacother 2005;6:1049-54.
46. Martı́nez-zaguilán R, Raghunand N, Lynch RM, et al. pH and drug resistance. I. functional expression of plasmalemmal V-type H+-ATPase in drug-resistant human breast carcinoma cell lines. Biochem Pharmacol 1999;57:1037-46.
47. Thews O, Gassner B, Kelleher DK, Schwerdt G, Gekle M. Impact of extracellular acidity on the activity of P-glycoprotein and the cytotoxicity of chemotherapeutic drugs. Neoplasia 2006;8:143-52.
48. Sauvant C, Nowak M, Wirth C, et al. Acidosis induces multi-drug resistance in rat prostate cancer cells (AT1) in vitro and in vivo by increasing the activity of the p-glycoprotein via activation of p38. Int J Cance ;123:2532-42.
49. Thews O, Dillenburg W, Fellner M, et al. Activation of P-glycoprotein (Pgp)-mediated drug efflux by extracellular acidosis: in vivo imaging with 68Ga-labelled PET tracer. Eur J Nucl Med Mol Imaging 2010;37:1935-42.
50. Thews O, Nowak M, Sauvant C, Gekle M. Hypoxia-induced extracellular acidosis increases p-glycoprotein activity and chemoresistance in tumors in vivo via p38 signaling pathway. Adv Exp Med Biol 2011;701:115-22.
51. Busa WB, Nuccitelli R. Metabolic regulation via intracellular pH. Am J Physiol 1984;246:R409-38.
53. Ma L, Center MS. The gene encoding vacuolar H+-ATPase subunit C is overexpressed in multidrug resistant HL60 cells. Biochem Biophys Res Commun 1992;182:675-81.
54. Chen Q, Liu Y, Zhu XL, et al. Increased NHE1 expression is targeted by specific inhibitor cariporide to sensitize resistant breast cancer cells to doxorubicin in vitro and in vivo. BMC cancer 20196;19:1-13.
55. Amith SR, Wilkinson JM, Baksh S, Fliegel L. The Na+/H+ exchanger (NHE1) as a novel co-adjuvant target in paclitaxel therapy of triple-negative breast cancer cells. Oncotarget 2015;6:1262-75.
56. Hoffmann EK, Lambert IH. Ion channels and transporters in the development of drug resistance in cancer cells. Philos Trans R Soc Lond B Biol Sci 2014;369:20130109.
57. Jin W, Lu Y, Li Q, et al. Down-regulation of the P-glycoprotein relevant for multidrug resistance by intracellular acidification through the crosstalk of MAPK signaling pathways. Int J Biochem Cell Biol 2014;54:111-21.
58. Wei LY, Roepe PD. Low external pH and osmotic shock increase the expression of human MDR protein. Biochemistry 1994;33:7229-38.
59. Kaufmann SH, Earnshaw WC. Induction of apoptosis by cancer chemotherapy. Exp Cell Res 2000;256:42-9.
60. Fulda S, Debatin KM. Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene 2006;25:4798-811.
63. Schmitt CA, Lowe SW. Apoptosis and chemoresistance in transgenic cancer models. J Mol Med (Berl) 2002;80:137-46.
64. Sergeeva TF, Shirmanova MV, Zlobovskaya OA, et al. Relationship between intracellular pH, metabolic co-factors and caspase-3 activation in cancer cells during apoptosis. Biochim Biophys Acta Mol Cell Res 2017;1864:604-11.
65. Morana S, Li J, Springer E, Eastman A. THe inhibition of etoposide-induced apoptosis by zinc is associated with modulation of intracellular pH. Int J Oncol 1994.
66. Matsuyama S, Llopis J, Deveraux QL, Tsien RY, Reed JC. Changes in intramitochondrial and cytosolic pH: early events that modulate caspase activation during apoptosis. Nat Cell Biol 2000;2:318-25.
67. Zhang S, Wang Y, Li SJ. Lansoprazole induces apoptosis of breast cancer cells through inhibition of intracellular proton extrusion. Biochem Biophys Res Commun 2014;448:424-9.
68. Harguindey S, Stanciu D, Devesa J, et al. Cellular acidification as a new approach to cancer treatment and to the understanding and therapeutics of neurodegenerative diseases. Semin Cancer Biol 2017;43:157-79.
69. Kim KY, Kim SH, Yu SN, et al. Salinomycin enhances doxorubicin-induced cytotoxicity in multidrug resistant MCF-7/MDR human breast cancer cells via decreased efflux of doxorubicin. Mol Med Rep 2015;12:1898-904.
70. Hermawan A, Wagner E, Roidl A. Consecutive salinomycin treatment reduces doxorubicin resistance of breast tumor cells by diminishing drug efflux pump expression and activity. Oncol Rep 2016;35:1732-40.
71. Dewangan J, Srivastava S, Rath SK. Salinomycin: a new paradigm in cancer therapy. Tumour Biol 2017;39:1010428317695035.
72. Dewangan J, Srivastava S, Rath SK. Salinomycin: a new paradigm in cancer therapy. Tumour Biol 2017;39:1010428317695035.
73. Riccioni R, Dupuis ML, Bernabei M, et al. The cancer stem cell selective inhibitor salinomycin is a p-glycoprotein inhibitor. Blood Cells Mol Dis 2010;45:86-92.
74. Koo KH, Kim H, Bae YK, et al. Salinomycin induces cell death via inactivation of Stat3 and downregulation of Skp2. Cell Death Dis 2013;4:e693.
75. Huczyński A, Janczak J, Antoszczak M, Wietrzyk J, Maj E, Brzezinski B. Antiproliferative activity of salinomycin and its derivatives. Bioorg Med Chem Lett 2012;22:7146-50.
76. Sommer AK, Hermawan A, Mickler FM, et al. Salinomycin co-treatment enhances tamoxifen cytotoxicity in luminal A breast tumor cells by facilitating lysosomal degradation of receptor tyrosine kinases. Oncotarget 2016;7:50461-76.
77. Lu D, Choi MY, Yu J, Castro JE, Kipps TJ, Carson DA. Salinomycin inhibits Wnt signaling and selectively induces apoptosis in chronic lymphocytic leukemia cells. Proc Natl Acad Sci ;108:13253-7.
78. Pellegrini P, Dyczynski M, Sbrana FV, et al. Tumor acidosis enhances cytotoxic effects and autophagy inhibition by salinomycin on cancer cell lines and cancer stem cells. Oncotarget 2016;7:35703-23.
79. Jiang J, Li H, Qaed E, et al. Salinomycin, as an autophagy modulator-- a new avenue to anticancer: a review. J Exp Clin Cancer Res 2018;37:26.
80. Yue W, Hamaï A, Tonelli G, et al. Inhibition of the autophagic flux by salinomycin in breast cancer stem-like/progenitor cells interferes with their maintenance. Autophagy 2013;9:714-29.
81. Antoszczak M. A medicinal chemistry perspective on salinomycin as a potent anticancer and anti-CSCs agent. Eur J Med Chem 2019;164:366-77.
82. Kaushik V, Yakisich JS, Kumar A, Azad N, Iyer AKV. Ionophores: potential use as anticancer drugs and chemosensitizers. Cancers (Basel) 2018;10:360.
83. Pallis M, Russell N. P-glycoprotein plays a drug-efflux-independent role in augmenting cell survival in acute myeloblastic leukemia and is associated with modulation of a sphingomyelin-ceramide apoptotic pathway. Blood 2000;95:2897-904.
84. Lu Y, Li QH, Ma L, et al. Effect of intracellular acidification on P-glycoprotein in drug-resistant K562/A02 cells. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2009;17:568-73.
85. Boscoboinik D, Gupta RS, Epand RM. Investigation of the relationship between altered intracellular pH and multidrug resistance in mammalian cells. Br J Cancer 1990;61:568-72.
86. Weisburg JH, Roepe PD, Dzekunov S, Scheinberg DA. Intracellular pH and multidrug resistance regulate complement-mediated cytotoxicity of nucleated human cells. J Biol Chem 1999;274:10877-88.
87. Belhoussine R, Morjani H, Sharonov S, Ploton D, Manfait M. Characterization of intracellular pH gradients in human multidrug-resistant tumor cells by means of scanning microspectrofluorometry and dual-emission-ratio probes. Int J Cancer 1999;81:81-9.
88. Epand RF, Epand RM, Gupta RS, Cragoe EJ Jr. Reversal of intrinsic multidrug resistance in Chinese hamster ovary cells by amiloride analogs. Br J Cancer 1991;63:247-51.
89. Pannocchia A, Revelli S, Tamponi G, et al. Reversal of doxorubicin resistance by the amiloride analogue EIPA in multidrug resistant human colon carcinoma cells. Cell Biochem Funct 1996;14:11-8.
90. Hamilton G, Cosentini EP, Teleky B, et al. The multidrug-resistance modifiers verapamil, cyclosporine A and tamoxifen induce an intracellular acidification in colon carcinoma cell lines in vitro. Anticancer Res 1993;13:2059-63.
91. Robinson LJ, Roberts WK, Ling TT, et al. Human MDR 1 protein overexpression delays the apoptotic cascade in Chinese hamster ovary fibroblasts. Biochemistry 1997;36:11169-78.
92. Smyth MJ, Krasovskis E, Sutton VR, Johnstone RW. The drug efflux protein, P-glycoprotein, additionally protects drug-resistant tumor cells from multiple forms of caspase-dependent apoptosis. Proc Natl Acad Sci U S A 1998;95:7024-9.
93. Taylor S, Spugnini EP, Assaraf YG, et al. Microenvironment acidity as a major determinant of tumor chemoresistance: Proton pump inhibitors (PPIs) as a novel therapeutic approach. Drug Resist Updat 2015;23:69-78.
94. Murakami T, Shibuya I, Ise T, et al. Elevated expression of vacuolar proton pump genes and cellular PH in cisplatin resistance. Int J Cancer 2001;93:869-74.
95. Thiebaut F, Currier SJ, Whitaker J, et al. Activity of the multidrug transporter results in alkalinization of the cytosol: measurement of cytosolic pH by microinjection of a pH-sensitive dye. J Histochem Cytochem 1990;38:685-90.
96. Hoffman MM, Wei LY, Roepe PD. Are altered pHi and membrane potential in hu MDR 1 transfectants sufficient to cause MDR protein-mediated multidrug resistance? J Gen Physiol 1996;108:295-313.
97. Stock C, Pedersen SF. Roles of pH and the Na+/H+ exchanger NHE1 in cancer: From cell biology and animal models to an emerging translational perspective? Semin Cancer Biol 2017;43:5-16.
98. Harguindey S, Arranz JL, Polo Orozco JD, et al. Cariporide and other new and powerful NHE1 inhibitors as potentially selective anticancer drugs--an integral molecular/biochemical/metabolic/clinical approach after one hundred years of cancer research. J Transl Med 2013;11:282.
99. Jin W, Li Q, Lin Y, et al. Reversal of Imatinib resistance in BCR-ABL-positive leukemia after inhibition of the Na+/H+ exchanger. Cancer Lett 2011;308:81-90.
100. Hu RH, Jin WN, Chang GQ, et al. Increasing sensitivity of leukemia cells to imatinib by inhibiting NHE1 and p38MAPK signaling pathway. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2012; 20:1341-5.
101. Lauritzen G, Jensen MB, Boedtkjer E, et al. NBCn1 and NHE1 expression and activity in DeltaNErbB2 receptor-expressing MCF-7 breast cancer cells: contributions to pHi regulation and chemotherapy resistance. Exp Cell Res 2010;316:2538-53.
102. Tavares-Valente D, Sousa B, Schmitt F, Baltazar F, Queirós O. Disruption of pH Dynamics Suppresses Proliferation and Potentiates Doxorubicin Cytotoxicity in Breast Cancer Cells. Pharmaceutics 2021;13:242.
103. Tonissen KF, Poulsen S. Carbonic anhydrase XII inhibition overcomes P-glycoprotein-mediated drug resistance: a potential new combination therapy in cancer. Cancer Drug Resist 2021;4:343-55.
104. von Neubeck B, Gondi G, Riganti C, et al. An inhibitory antibody targeting carbonic anhydrase XII abrogates chemoresistance and significantly reduces lung metastases in an orthotopic breast cancer model in vivo. Int J Cancer 2018;143:2065-75.
105. Kopecka J, Rankin GM, Salaroglio IC, Poulsen SA, Riganti C. P-glycoprotein-mediated chemoresistance is reversed by carbonic anhydrase XII inhibitors. Oncotarget 2016;7:85861-75.
106. Zheng G, Peng C, Jia X, et al. ZEB1 transcriptionally regulated carbonic anhydrase 9 mediates the chemoresistance of tongue cancer via maintaining intracellular pH. Mol Cancer 2015;14:84.
107. Podolski-Renić A, Dinić J, Stanković T, et al. Sulfocoumarins, specific carbonic anhydrase IX and XII inhibitors, interact with cancer multidrug resistant phenotype through pH regulation and reverse P-glycoprotein mediated resistance. Eur J Pharm Sci 2019;138:105012.
108. Ilardi G, Zambrano N, Merolla F, et al. Histopathological determinants of tumor resistance: a special look to the immunohistochemical expression of carbonic anhydrase IX in human cancers. Curr Med Chem 2014;21:1569-82.
109. Lu Y, Pang T, Wang J, et al. Down-regulation of P-glycoprotein expression by sustained intracellular acidification in K562/Dox cells. Biochem Biophys Res Commun 2008;377:441-6.
110. Li Y, Xiang J, Zhang SS, et al. Analysis of the impact of extracellular acidity on the expression and activity of P-glycoprotein and on the P-glycoprotein-mediated cytotoxicity of daunorubicin in cancer cell by microfluidic chip technology. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2015;37:75-81.
111. Young G, Reuss L, Altenberg GA. Altered intracellular pH regulation in cells with high levels of P-glycoprotein expression. I. nt J Biochem Mol Biol 2011;2:219-27.
112. Coley HM, Labeed FH, Thomas H, Hughes MP. Biophysical characterization of MDR breast cancer cell lines reveals the cytoplasm is critical in determining drug sensitivity. Biochim Biophys Acta 2007;1770:601-8.
113. Mulhall HJ, Cardnell A, Hoettges KF, Labeed FH, Hughes MP. Apoptosis progression studied using parallel dielectrophoresis electrophysiological analysis and flow cytometry. Integr Biol (Camb) 2015;7:1396-401.
114. Wei L, Stutts M, Hoffman M, Roepe P. Overexpression of the cystic fibrosis transmembrane conductance regulator in NIH 3T3 cells lowers membrane potential and intracellular pH and confers a multidrug resistance phenotype. Biophys J 1995;69:883-95.
115. Miraglia E, Viarisio D, Riganti C, Costamagna C, Ghigo D, Bosia A. Na+/H+ exchanger activity is increased in doxorubicin-resistant human colon cancer cells and its modulation modifies the sensitivity of the cells to doxorubicin. Int J Cancer 2005;115:924-9.
116. Li S, Bao P, Li Z, Ouyang H, Wu C, Qian G. Inhibition of proliferation and apoptosis induced by a Na+/H+ exchanger-1 (NHE-1) antisense gene on drug-resistant human small cell lung cancer cells. Oncol Rep 2009;21:1243-9.
117. Omran Z, Whitehouse C, Halwani M, et al. Pinocytosis as the biological mechanism that protects PGP function in multidrug resistant cancer cells and in blood-brain barrier endothelial cells. Symmetry 2020;12:1221.
118. Petelska AD, Figaszewski ZA. Interfacial tension of bilayer lipid membrane formed from phosphatidylethanolamine. Biochim Biophys Acta 2002;1567:79-86.
119. Schuldes H, Dolderer J, Zimmer G, et al. Reversal of multidrug resistance and increase in plasma membrane fluidity in CHO cells with R-verapamil and bile salts. Eur J Cancer 2001;37:660-7.
120. Drori S, Eytan GD, Assaraf YG. Potentiation of anticancer-drug cytotoxicity by multidrug-resistance chemosensitizers involves alterationsin membrane fluidity leading to increased membrane permeability. Eur J Biochem 1995;228:1020-9.
121. Regev R, Katzir H, Yeheskely-Hayon D, Eytan GD. Modulation of P-glycoprotein-mediated multidrug resistance by acceleration of passive drug permeation across the plasma membrane. FEBS J 2007;274:6204-14.
122. Ferté J. Analysis of the tangled relationships between P-glycoprotein-mediated multidrug resistance and the lipid phase of the cell membrane. Eur J Biochem 2000;267:277-94.
123. Zong L, Pi Z, Liu S, Xing J, Liu Z, Song F. Liquid extraction surface analysis nanospray electrospray ionization based lipidomics for in situ analysis of tumor cells with multidrug resistance. Rapid Commun Mass Spectrom 2018;32:1683-92.
124. Leibovici J, Klein O, Wollman Y, et al. Cell membrane fluidity and adriamycin retention in a tumor progression movel of AKR lymphoma. Biochim Biophys Acta 1996;1281:182-8.
125. Zhang H, Yao M, Morrison RA, Chong S. Commonly used surfactant, Tween 80, improves absorption of P-glycoprotein substrate, digoxin, in rats. Arch Pharm Res 2003;26:768-72.
126. Kaur P, Garg T, Rath G, Murthy RS, Goyal AK. Surfactant-based drug delivery systems for treating drug-resistant lung cancer. Drug Deliv 2016;23:727-38.
127. Tsuruo T, Iida H, Tsukagoshi S, Sakurai Y. Overcoming of vincristine resistance in P388 leukemia, in vivo and in vitro through enhanced cytoloxicity of vincristine and vinblastine by verapamil. Cancer Res 1981;41:1967-72.
128. Muller C, Goubin F, Ferrandis E, et al. Evidence for transcriptional control of human mdr1 gene expression by verapamil in multidrug-resistant leukemic cells. Mol Pharmacol 1995;47:51-6.
129. Broxterman HJ, Pinedo HM, Kuiper CM, et al. Induction by verapamil of a rapid increase in ATP consumption in multidrug-resistant tumor cells. FASEB J 1988;2:2278-82.
130. Yusa K, Tsuruo T. Reversal mechanism of multidrug resistance by verapamil: direct binding of verapamil to P-glycoprotein on specific sites and transport of verapamil outward across the plasma membrane of K562/ADM cells. Cancer Res 1989;49:5002-6. Available from:
131. Salmon S, Dalton W, Grogan T, et al. Multidrug-resistant myeloma: laboratory and clinical effects of verapamil as a chemosensitizer. Blood 1991;78:44-50.
132. Karwatsky J, Lincoln MC, Georges E. A mechanism for P-glycoprotein-mediated apoptosis as revealed by verapamil hypersensitivity. Biochemistry 2003;42:12163-73.
133. Warr JR, Anderson, M, Fergusson J. Properties of verapamil-hypersensitive multidrug-resistant Chinese hamster ovary cells. Cancer Res 1988;48:4477-83.
134. Dönmez Y, Akhmetova L, İşeri ÖD, Kars MD, Gündüz U. Effect of MDR modulators verapamil and promethazine on gene expression levels of MDR1 and MRP1 in doxorubicin-resistant MCF-7 cells. Cancer Chemother Pharmacol 2011;67:823-8.
135. Afrooz H, Ahmadi F, Fallahzadeh F, Mousavi-fard SH, Alipour S. Design and characterization of paclitaxel-verapamil co-encapsulated PLGA nanoparticles: Potential system for overcoming P-glycoprotein mediated MDR. Journal of Drug Delivery Science and Technology 2017;41:174-81.
136. Williams JB, Buchanan CM, Pitt WG. Codelivery of doxorubicin and verapamil for treating multidrug resistant cancer cells. Pharm Nanotechnol 2018;6:116-23.
137. Wang L, Sun Y. Efflux mechanism and pathway of verapamil pumping by human P-glycoprotein. Arch Biochem Biophys 2020;696:108675.
138. Woodcock DM, Linsenmeyer ME, Chojnowski G, et al. Reversal of multidrug resistance by surfactants. Br J Cancer 1992;66:62-8.
139. Yuan X, Ji W, Chen S, et al. A novel paclitaxel-loaded poly(d,l-lactide-co-glycolide)-Tween 80 copolymer nanoparticle overcoming multidrug resistance for lung cancer treatment. Int J Nanomedicine 2016;11:2119-31.
140. Kaur H, Ghosh S, Kumar P, Basu B, Nagpal K. Ellagic acid-loaded, tween 80-coated, chitosan nanoparticles as a promising therapeutic approach against breast cancer: In-vitro and in-vivo study. Life Sci 2021;284:119927.
141. Bhattacharjee J, Verma G, Aswal VK, et al. Tween 80-sodium deoxycholate mixed micelles: structural characterization and application in doxorubicin delivery. J Phys Chem B 2010;114:16414-21.
142. Tsujino I, Yamazaki T, Masutani M, Sawada U, Horie T. Effect of Tween-80 on cell killing by etoposide in human lung adenocarcinoma cells. Cancer Chemother Pharmacol 1999;43:29-34.
143. Neri D, Supuran CT. Interfering with pH regulation in tumours as a therapeutic strategy. Nat Rev Drug Discov 2011;10:767-77.
144. Diego J P, Trilla C, Cañero RG. Potentiation by amiloride of doxorubicin effect on normal and tumor liver cells in vitro. International Hepatology Communications 1995;3:S165. Available from:
145. Matthews H, Ranson M, Kelso MJ. Anti-tumour/metastasis effects of the potassium-sparing diuretic amiloride: an orally active anti-cancer drug waiting for its call-of-duty? Int J Cancer 2011;129:2051-61.
146. Xu S, Liu C, Ma Y, Ji HL, Li X. Potential roles of amiloride-sensitive sodium channels in cancer development. Biomed Res Int 2016;2016:2190216.
147. Zheng YT, Yang HY, Li T, et al. Amiloride sensitizes human pancreatic cancer cells to erlotinib in vitro through inhibition of the PI3K/AKT signaling pathway. Acta Pharmacol Sin 2015;36:614-26.
148. Rojas EA, Corchete LA, San-Segundo L, et al. Amiloride, an old diuretic drug, is a potential therapeutic agent for multiple myeloma. Clin Cancer Res 2017;23:6602-15.
149. Cho YL, Lee KS, Lee SJ, et al. Amiloride potentiates TRAIL-induced tumor cell apoptosis by intracellular acidification-dependent Akt inactivation. Biochem Biophys Res Commun 2005;326:752-8.
150. Chang WH, Liu TC, Yang WK, et al. Amiloride modulates alternative splicing in leukemic cells and resensitizes Bcr-AblT315I mutant cells to imatinib. Cancer Res 2011;71:383-92.
151. Matthews H, Ranson M, Tyndall JD, Kelso MJ. Synthesis and preliminary evaluation of amiloride analogs as inhibitors of the urokinase-type plasminogen activator (uPA). Bioorg Med Chem Lett 2011;21:6760-6.
152. Wang Y, Dang J, Liang X, Doe WF. Amiloride modulates urokinase gene expression at both transcription and post-transcription levels in human colon cancer cells. Clin Exp Metastasis 1995;13:196-202.
153. Jankun J, Skrzypczak-Jankun E. Molecular basis of specific inhibition of urokinase plasminogen activator by amiloride. Cancer biochem biophys 1999;17:109-23.
154. Buckley BJ, Kumar A, Aboelela A, et al. Screening of 5- and 6-substituted amiloride libraries identifies dual-uPA/NHE1 active and single target-selective inhibitors. Int J Mol Sci 2021;22:2999.
155. Zhou L, Zhang T, Shao W, et al. Amiloride ameliorates muscle wasting in cancer cachexia through inhibiting tumor-derived exosome release. Skelet Muscle 2021;11:17.
156. Chalmin F, Ladoire S, Mignot G, et al. Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells. J Clin Invest 2010;120:457-71.
157. Dorayappan KDP, Wanner R, Wallbillich JJ, et al. Hypoxia-induced exosomes contribute to a more aggressive and chemoresistant ovarian cancer phenotype: a novel mechanism linking STAT3/Rab proteins. Oncogene 2018;37:3806-21.
158. Escrevente C, Keller S, Altevogt P, Costa J. Interaction and uptake of exosomes by ovarian cancer cells. BMC Cancer 2011;11:108.
159. Diego JP, Trilla C, Cañero RG. Involvement of the activity of the MDR gene product, GP170, with PH I regulation in rat hepatoma cells in vitro. I. nternational Hepatology Communications 1995;3:S166. Available from:
160. Radvakóva I, Mirossay A, Mojzis J, Mirossay L. The effect of 5’-(N, N-dimethyl)-amiloride on cytotoxic activity of doxorubicin and vincristine in CEM cell lines. Physiol Res 2001;50:283-8.
162. Garcãa-caã±ero R. Transport activity of the multidrug resistance protein is accompanied by amiloride-sensitive intracellular pH changes in rat hepatoma cells. Hepatology Research 1998;10:27-40.
163. Geers C, Gros G. Effects of carbonic anhydrase inhibitors on contraction, intracellular pH and energy-rich phosphates of rat skeletal muscle. J Physiol 1990;423:279-97.
164. Swietach P, Patiar S, Supuran CT, Harris AL, Vaughan-Jones RD. The role of carbonic anhydrase 9 in regulating extracellular and intracellular ph in three-dimensional tumor cell growths. J Biol Chem 2009;284:20299-310.
165. Chiche J, Ilc K, Laferrière J, et al. Hypoxia-inducible carbonic anhydrase IX and XII promote tumor cell growth by counteracting acidosis through the regulation of the intracellular pH. Cancer Res 2009;69:358-68.
166. Bin K, Shi-Peng Z. Acetazolamide inhibits aquaporin-1 expression and colon cancer xenograft tumor growth. Hepatogastroenterology 2011;58:1502-6.
167. Parkkila S, Rajaniemi H, Parkkila AK, et al. Carbonic anhydrase inhibitor suppresses invasion of renal cancer cells in vitro. Proc Natl Acad Sci ;97:2220-4.
168. Duan L, Di Q. Acetazolamide suppresses multi-drug resistance-related protein 1 and p-glycoprotein expression by inhibiting aquaporins expression in a mesial temporal epilepsy rat model. Med Sci Monit 2017;23:5818-25.
169. Zheng G, Zhou M, Ou X, et al. Identification of carbonic anhydrase 9 as a contributor to pingyangmycin-induced drug resistance in human tongue cancer cells. FEBS J 2010;277:4506-18.
170. Kopecka J, Campia I, Jacobs A, et al. Carbonic anhydrase XII is a new therapeutic target to overcome chemoresistance in cancer cells. Oncotarget 2015;6:6776-93.
171. Teodori E, Braconi L, Bua S, et al. Dual P-glycoprotein and CA XII inhibitors: a new strategy to reverse the P-gp mediated multidrug resistance (MDR) in cancer cells. Molecules 2020;25:1748.
172. Zhao X, Zhang N, Huang Y, et al. Lansoprazole alone or in combination with gefitinib shows antitumor activity against non-small cell lung cancer a549 cells in vitro and in vivo. Front Cell Dev Biol 2021;9:655559.
173. Huntington KE, Louie A, Zhou L, et al. Colorectal cancer extracellular acidosis decreases immune cell killing and is partially ameliorated by pH-modulating agents that modify tumor cell cytokine profiles. Am J Cancer Res 2022;12:138-51.
174. Azzarito T, Venturi G, Cesolini A, Fais S. Lansoprazole induces sensitivity to suboptimal doses of paclitaxel in human melanoma. Cancer Lett 2015;356:697-703.
175. Yu M, Lee C, Wang M, Tannock IF. Influence of the proton pump inhibitor lansoprazole on distribution and activity of doxorubicin in solid tumors. Cancer Sci 2015;106:1438-47.
176. Goh W, Sleptsova-Freidrich I, Petrovic N. Use of proton pump inhibitors as adjunct treatment for triple-negative breast cancers. An introductory study. J Pharm Pharm Sci 2014;17:439-46.
177. Hansen AR, Tannock IF, Templeton A, et al. Pantoprazole Affecting Docetaxel Resistance Pathways Via Autophagy (PANDORA): phase II trial of high dose pantoprazole (autophagy inhibitor) with docetaxel in metastatic castration-resistant prostate cancer (mCRPC). Oncologist 2019;24:1188-94.
178. Li Z, He P, Long Y, et al. Drug repurposing of pantoprazole and vitamin c targeting tumor microenvironment conditions improves anticancer effect in metastatic castration-resistant prostate cancer. Front Oncol 2021;11:660320.
179. Lu ZN, Shi ZY, Dang YF, et al. Pantoprazole pretreatment elevates sensitivity to vincristine in drug-resistant oral epidermoid carcinoma in vitro and in vivo. Biomed Pharmacother 2019;120:109478.
180. Tvingsholm SA, Dehlendorff C, Østerlind K, Friis S, Jäättelä M. Proton pump inhibitor use and cancer mortality. Int J Cancer 2018;143:1315-26.
181. Wang X, Liu C, Wang J, Fan Y, Wang Z, Wang Y. Proton pump inhibitors increase the chemosensitivity of patients with advanced colorectal cancer. Oncotarget 2017;8:58801-8.
182. Federici C, Petrucci F, Caimi S, et al. Exosome release and low pH belong to a framework of resistance of human melanoma cells to cisplatin. PLoS One 2014;9:e88193.
183. Luciani F, Spada M, De Milito A, et al. Effect of proton pump inhibitor pretreatment on resistance of solid tumors to cytotoxic drugs. J Natl Cancer Inst 2004;96:1702-13.
184. Wang BY, Zhang J, Wang JL, et al. Intermittent high dose proton pump inhibitor enhances the antitumor effects of chemotherapy in metastatic breast cancer. J Exp Clin Cancer Res 2015;34:85.
185. Tavana E, Mollazadeh H, Mohtashami E, et al. Quercetin: a promising phytochemical for the treatment of glioblastoma multiforme. Biofactors 2020;46:356-66.
186. Shim CK, Cheon EP, Kang KW, Seo KS, Han HK. Inhibition effect of flavonoids on monocarboxylate transporter 1 (MCT1) in Caco-2 cells. J Pharm Pharmacol 2007;59:1515-9.
187. Albatany M, Meakin S, Bartha R. The monocarboxylate transporter inhibitor quercetin induces intracellular acidification in a mouse model of glioblastoma multiforme: in-vivo detection using magnetic resonance imaging. Invest New Drugs 2019;37:595-601.
188. Borska S, Chmielewska M, Wysocka T, Drag-Zalesinska M, Zabel M, Dziegiel P. In vitro effect of quercetin on human gastric carcinoma: targeting cancer cells death and MDR. Food Chem Toxicol 2012;50:3375-83.
189. Li S, Zhao Q, Wang B, et al. Quercetin reversed MDR in breast cancer cells through down-regulating P-gp expression and eliminating cancer stem cells mediated by YB-1 nuclear translocation. Phytother Res 2018;32:1530-6.
190. Kumar M, Sharma G, Misra C, et al. N-desmethyl tamoxifen and quercetin-loaded multiwalled CNTs: a synergistic approach to overcome MDR in cancer cells. Mater Sci Eng C Mater Biol Appl 2018;89:274-82.
191. Liu M, Fu M, Yang X, et al. Paclitaxel and quercetin co-loaded functional mesoporous silica nanoparticles overcoming multidrug resistance in breast cancer. Colloids Surf B Biointerfaces 2020;196:111284.
192. Zhou Y, Zhang J, Wang K, et al. Quercetin overcomes colon cancer cells resistance to chemotherapy by inhibiting solute carrier family 1, member 5 transporter. Eur J Pharmacol 2020;881:173185.
193. Marques MB, Machado AP, Santos PA, et al. Anti-MDR effects of quercetin and its nanoemulsion in multidrug-resistant human leukemia cells. Anticancer Agents Med Chem 2021;21:1911-20.
194. Liu S, Li R, Qian J, et al. Combination therapy of doxorubicin and quercetin on multidrug-resistant breast cancer and their sequential delivery by reduction-sensitive hyaluronic acid-based conjugate/d-α-tocopheryl poly(ethylene glycol) 1000 succinate mixed micelles. Mol Pharm 2020;17:1415-27.
195. Liu Z, Balasubramanian V, Bhat C, et al. Quercetin-based modified porous silicon nanoparticles for enhanced inhibition of doxorubicin-resistant cancer cells. Adv Healthc Mater 2017;6:1601009.
196. Lv L, Liu C, Chen C, et al. Quercetin and doxorubicin co-encapsulated biotin receptor-targeting nanoparticles for minimizing drug resistance in breast cancer. Oncotarget 2016;7:32184-99.
197. Chen C, Zhou J, Ji C. Quercetin: a potential drug to reverse multidrug resistance. Life Sci 2010;87:333-8.
198. Scambia G, Ranelletti FO, Panici PB, et al. Quercetin potentiates the effect of adriamycin in a multidrug-resistant MCF-7 human breast-cancer cell line: P-glycoprotein as a possible target. Cancer Chemother Pharmacol 1994;34:459-64.
199. Iriti M, Kubina R, Cochis A, et al. Rutin, a quercetin glycoside, restores chemosensitivity in human breast cancer cells. Phytother Res 2017;31:1529-38.
200. Limtrakul P, Khantamat O, Pintha K. Inhibition of P-glycoprotein function and expression by kaempferol and quercetin. J Chemother 2005;17:86-95.
201. Chen Z, Huang C, Ma T, et al. Reversal effect of quercetin on multidrug resistance via FZD7/β-catenin pathway in hepatocellular carcinoma cells. Phytomedicine 2018;43:37-45.
202. Yuan Z, Wang H, Hu Z, et al. Quercetin inhibits proliferation and drug resistance in KB/VCR oral cancer cells and enhances its sensitivity to vincristine. Nutr Cancer 2015;67:126-36.
203. Daglioglu C. Enhancing tumor cell response to multidrug resistance with PH-sensitive quercetin and doxorubicin conjugated multifunctional nanoparticles. Colloids Surf B Biointerfaces 2017;156:175-85.
204. Kim SH, Yeo GS, Lim YS, et al. Suppression of multidrug resistance via inhibition of heat shock factor by quercetin in MDR cells. Exp Mol Med 1998;30:87-92.
205. Zhang J, Luo Y, Zhao X, et al. Co-delivery of doxorubicin and the traditional Chinese medicine quercetin using biotin-PEG2000-DSPE modified liposomes for the treatment of multidrug resistant breast cancer. RSC Adv 2016;6:113173-84.
206. Singh A, Patel SK, Kumar P, et al. Quercetin acts as a P-gp modulator via impeding signal transduction from nucleotide-binding domain to transmembrane domain. J Biomol Struct Dyn 2020:1-9.
207. Chen FY, Cao LF, Wan HX, et al. Quercetin enhances adriamycin cytotoxicity through induction of apoptosis and regulation of mitogen-activated protein kinase/extracellular signal-regulated kinase/c-Jun N-terminal kinase signaling in multidrug-resistant leukemia K562 cells. Mol Med Rep 2015;11:341-8.
208. Czepas J, Gwoździński K. The flavonoid quercetin: possible solution for anthracycline-induced cardiotoxicity and multidrug resistance. Biomed Pharmacother 2014;68:1149-59.
209. Maruszewska A, Tarasiuk J. Quercetin triggers induction of apoptotic and lysosomal death of sensitive and multidrug resistant leukaemia HL60 cells. Nutr Cancer 2021;73:484-501.
210. Xu W, Xie S, Chen X, Pan S, Qian H, Zhu X. Effects of quercetin on the efficacy of various chemotherapeutic drugs in cervical cancer cells. Drug Des Devel Ther 2021;15:577-88.
211. Kim MK, Choo H, Chong Y. Water-soluble and cleavable quercetin-amino acid conjugates as safe modulators for P-glycoprotein-based multidrug resistance. J Med Chem 2014;57:7216-33.
212. Yuan J, Wong IL, Jiang T, et al. Synthesis of methylated quercetin derivatives and their reversal activities on P-gp- and BCRP-mediated multidrug resistance tumour cells. Eur J Med Chem 2012;54:413-22.
213. Choiprasert W, Dechsupa N, Kothan S, Garrigos M, Mankhetkorn S. Quercetin, quercetrin except rutin potentially increased pirarubicin cytotoxicity by non-competitively inhibiting the P-glycoprotein-and MRP1 function in living K562/adr and GLC4/adr cells. American Journal of Pharmacology and Toxicology 2010;5:24-33. Available from:
214. Kim MK, Park KS, Choo H, Chong Y. Quercetin-POM (pivaloxymethyl) conjugates: Modulatory activity for P-glycoprotein-based multidrug resistance. Phytomedicine 2015;22:778-85.
215. Hyun HB, Moon JY, Cho SK. Quercetin suppresses CYR61-mediated multidrug resistance in human gastric adenocarcinoma AGS cells. Molecules 2018;23:209.
216. Cho CJ, Yu CP, Wu CL, et al. Decreased drug resistance of bladder cancer using phytochemicals treatment. Kaohsiung J Med Sci 2021;37:128-35.
217. Lu X, Yang F, Chen D, et al. Quercetin reverses docetaxel resistance in prostate cancer via androgen receptor and PI3K/Akt signaling pathways. Int J Biol Sci 2020;16:1121-34.
218. Amorim R, Pinheiro C, Miranda-Gonçalves V, et al. Monocarboxylate transport inhibition potentiates the cytotoxic effect of 5-fluorouracil in colorectal cancer cells. Cancer Lett 2015;365:68-78.
219. Andres S, Pevny S, Ziegenhagen R, et al. Safety aspects of the use of quercetin as a dietary supplement. Mol Nutr Food Res 2018;62:1700447.
220. Gulati N, Laudet B, Zohrabian VM, Murali R, Jhanwar-Uniyal M. The antiproliferative effect of quercetin in cancer cells is mediated via inhibition of the PI3K-Akt/PKB pathway. Anticancer Res 2006;26:1177-81. Available from:
221. Bruning A. Inhibition of mTOR signaling by quercetin in cancer treatment and prevention. Anticancer Agents Med Chem 2013;13:1025-31.
222. Klappan AK, Hones S, Mylonas I, Brüning A. Proteasome inhibition by quercetin triggers macroautophagy and blocks mTOR activity. Histochem Cell Biol 2012;137:25-36.
223. Wang K, Liu R, Li J, et al. Quercetin induces protective autophagy in gastric cancer cells: involvement of Akt-mTOR- and hypoxia-induced factor 1α-mediated signaling. Autophagy 2011;7:966-78.
224. Maurya AK, Vinayak M. Modulation of PKC signaling and induction of apoptosis through suppression of reactive oxygen species and tumor necrosis factor receptor 1 (TNFR1): key role of quercetin in cancer prevention. Tumour Biol 2015;36:8913-24.
225. Jeong JH, An JY, Kwon YT, Rhee JG, Lee YJ. Effects of low dose quercetin: cancer cell-specific inhibition of cell cycle progression. J Cell Biochem 2009;106:73-82.
226. Yoshida M, Sakai T, Hosokawa N, et al. The effect of quercetin on cell cycle progression and growth of human gastric cancer cells. FEBS Letters 1990;260:10-3.
227. Aalinkeel R, Bindukumar B, Reynolds JL, et al. The dietary bioflavonoid, quercetin, selectively induces apoptosis of prostate cancer cells by down - regulating the expression of heat shock protein 90. Prostate 2008;68:1773-89.
228. Park CH, Chang JY, Hahm ER, et al. Quercetin, a potent inhibitor against beta-catenin/Tcf signaling in SW480 colon cancer cells. Biochem Biophys Res Commun 2005;328:227-34.
229. Russo GL, Russo M, Spagnuolo C, et al. Quercetin: a Pleiotropic Kinase Inhibitor Against Cancer. In: Zappia V, Panico S, Russo GL, Budillon A, Della Ragione F, editors. Advances in Nutrition and Cancer. Berlin: Springer Berlin Heidelberg; 2014. p. 185-205.
230. Choi JA, Kim JY, Lee JY, et al. Induction of cell cycle arrest and apoptosis in human breast cancer cells by quercetin. Int J Oncol 2001;19:837-44.
231. Marathe K, McVicar N, Li A, et al. Topiramate induces acute intracellular acidification in glioblastoma. J Neurooncol 2016;130:465-72.
232. Bonnet U, Wiemann M. Topiramate decelerates bicarbonate-driven acid-elimination of human neocortical neurons: strategic significance for its antiepileptic, antimigraine and neuroprotective properties. CNS Neurol Disord Drug Targets 2020;19:264-75.
233. K. Y. Intracellular Acidification in brain tumors induced by topiramate: in-vivo detection using chemical exchange saturation transfer magnetic resonance imaging. Electronic Thesis and Dissertation Repository ;Available from:
234. Albatany M, Ostapchenko VG, Meakin S, Bartha R. Brain tumor acidification using drugs simultaneously targeting multiple pH regulatory mechanisms. J Neurooncol 2019;144:453-62.
235. Leniger T, Thöne J, Wiemann M. Topiramate modulates pH of hippocampal CA3 neurons by combined effects on carbonic anhydrase and Cl-/HCO3- exchange. Br J Pharmacol 2004;142:831-42.
236. Feldmann M, Asselin M, Liu J, et al. P-glycoprotein expression and function in patients with temporal lobe epilepsy: a case-control study. Lancet Neurol 2013;12:777-85.
237. Stępień KM, Tomaszewski M, Tomaszewska J, Czuczwar SJ. The multidrug transporter P-glycoprotein in pharmacoresistance to antiepileptic drugs. Pharmacoll Rep 2012;64:1011-9.
238. Balza E, Carlone S, Carta S, et al. Therapeutic efficacy of proton transport inhibitors alone or in combination with cisplatin in triple negative and hormone sensitive breast cancer models. Cancer Med 2022;11:183-93.
239. Heilos D, Röhrl C, Pirker C, et al. Altered membrane rigidity via enhanced endogenous cholesterol synthesis drives cancer cell resistance to destruxins. Oncotarget 2018;9:25661-80.
240. Inci F, Celik U, Turken B, Özer HÖ, Kok FN. Construction of P-glycoprotein incorporated tethered lipid bilayer membranes. Biochem Biophys Rep 2015;2:115-22.
