2,235
Views
221
CrossRef citations to date
0
Altmetric
Review Article

Molecular mechanisms of drug resistance and its reversal in cancer

, &
Pages 716-726 | Received 05 Oct 2013, Accepted 21 Dec 2014, Published online: 11 Mar 2015

References

  • Adan-Gokbulut A, Kartal-Yandim M, Iskender G, Baran Y. (2013). Novel agents targeting bioactive sphingolipids for the treatment of cancer. Curr Med Chem, 20, 108–22
  • Ali IU, Schriml LM, Dean M. (1999). Mutational spectra of PTEN/MMAC1 gene: a tumor suppressor with lipid phosphatase activity. J Natl Cancer Inst, 91, 1922–32
  • Ambudkar SV, Dey S, Hrycyna CA, et al. (1999). Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annu Rev Pharmacol Toxicol, 39, 361–98
  • Annereau JP, Szakács G, Tucker CJ, et al. (2004). Analysis of ATP-binding cassette transporter expression in drug-selected cell lines by a microarray dedicated to multidrug resistance. Mol Pharmacol, 66, 1397–405
  • Balkin ER, Jia F, Miller WH, Lewis MR. (2011). In vitro evaluation of targeted antisense 177Lu radiotherapy. Anticancer Res, 31, 3143–9
  • Barker CJ, Bowler K. (1991). Lipid composition of the membranes from cells of two rat tumors and its relationship to tumor thermosensitivity. Radiat Res, 125, 48–55
  • Bektas M, Jolly PS, Müller C, et al. (2005). Sphingosine kinase activity counteracts ceramide-mediated cell death in human melanoma cells: role of Bcl-2 expression. Oncogene, 24, 178–87
  • Bode AM, Dong Z. (2004). Post-translational modification of p53 in tumorigenesis. Nat Rev Cancer, 4, 793–805
  • Bogman K, Peyer AK, Török M, et al. (2001). HMG-CoAreductase inhibitors and P-glycoprotein modulation. Br J Pharmacol, 132, 1183–92
  • Borst P. (1991). Genetic mechanisms of drug resistance: a review. Acta Oncol, 30, 87–105
  • Borst P, Evers R, Kool M, Wijnholds J. (2000). A family of drug transporters: the multidrug resistance-associated proteins. J Natl Cancer Inst, 92, 1295–301
  • Campos L, Guyotat D, Archimbaud E, et al. (1992). Clinical significance of multidrug resistance P-glycoprotein expression on acute nonlymphoblastic leukemia cells at diagnosis. Blood, 79, 473–6
  • Castaing M, Brouant P, Loiseau A, et al. (2000). Membrane permeation by multidrug-resistance-modulators and non-modulators: effects of hydrophobicity and electric charge. J Pharm Pharmacol, 52, 289–96
  • Chang EH, Pirollo KF, Bouker KB. (2000). Tp53 gene therapy: a key to modulating resistance to anticancer therapies? Mol Med Today, 6, 358–64
  • Chauhan PS, Bhushan B, Singh LC, et al. (2012). Expression of genes related to multiple drug resistance and apoptosis in acute leukemia: response to induction chemotherapy. Exp Mol Pathol, 92, 44–9
  • Choi CH. (2005). ABC transporters as multidrug resistance mechanisms and the development of chemosensitizers for their reversal. Cancer Cell Int, 30, 1–13
  • Cuestas ML, Sosnik A, Mathet V. (2011). Poloxamines display a multiple inhibitory activity of ATP-Binding Cassette (ABC) transporters in cancer cell lines. Mol Pharm, 8, 1152–64
  • Daniel C, Bell C, Burton C, et al. (2013). The role of proton dynamics in the development and maintenance of multidrug resistance in cancer. Biochimica et Biophysica Acta, 1832, 606–17
  • Das M, Sahoo SK. (2012). Folate decorated dual drug loaded nanoparticle: role of curcumin in enhancing therapeutic potential of nutlin-3a by reversing multidrug resistance. PLoS One, 7, e32920
  • Dean M, Rzhetsky A, Alliknets R. (2001). The human ATP-binding cassette (ABC) transporter superfamily. Genome Res, 11, 1156–66
  • Demant EJ, Sehested M, Jensen PB. (1990). A model for computer simulation of P-glycoprotein and transmembrane delta pH-mediated transport in multidrug-resistant tumor cells. Biochim Biophys Acta, 1055, 117–25
  • Dönmez Y, Gündüz U. (2011). Reversal of multidrug resistance by small interfering RNA (siRNA) in doxorubicin-resistant MCF-7 breast cancer cells. Biomed Pharmacother, 65, 85–9
  • Doudican NA, Byron SA, Pollock PM, Orlow SJ. (2013). XIAP downregulation accompanies mebendazole growth inhibition in melanoma xenografts. Anticancer Drugs, 24, 181–8
  • Duvvuri M, Krise JP. (2005). Intracellular drug sequestration events associated with the emergence of multidrug resistance: a mechanistic review. Front Biosci, 10, 1499–509
  • Eid SY, El-Readi MZ, Eldin EE, et al. (2013). Influence of combinations of digitonin with selected phenolics, terpenoids, and alkaloids on the expression and activity of P-glycoprotein in leukaemia and colon cancer cells. Phytomedicine, 21, 47–61
  • Fujita T, Doihara H, Washio K, et al. (2006). Proteasome inhibitor bortezomib increases PTEN expression and enhances trastuzumab-induced growth inhibition in trastuzumab-resistant cells. Anticancer Drugs, 17, 455–62
  • Gawryluk JW, Wang JF, Andreazza AC, et al. (2011). Decreased levels of glutathione, the major brain antioxidant, in post-mortem prefrontal cortex from patients with psychiatric disorders. Int J Neuropsychopharmacol, 14, 123–30
  • George SR, Ng GY, Lee SP, et al. (2003). Blockade of G protein-coupled receptors and the dopamine transporter by a transmembrane domain peptide: novel strategy for functional inhibition of membrane proteins in vivo. J Pharmacol Exp Ther, 307, 481–9
  • Giaccone G, Pinedo HM. (1996). Drug resistance. Oncologist, 1, 82–7
  • Goldstein LJ, Galski H, Fojo A, et al. (1989). Expression of a multidrug resistance gene in human cancers. J Natl Cancer Inst, 81, 116–24
  • Gottesman MM. (2002). Mechanisms of cancer drug resistance. Ann Rev Med, 53, 615–27
  • Gouazé V, Liu YY, Prickett CS, et al. (2005). Glucosylceramide synthase blockade down-regulates P-glycoprotein and resensitizes multidrug-resistant breast cancer cells to anticancer drugs. Cancer Res, 65, 3861–7
  • Grant CE, Valdimarsson G, Hipfner DR, et al. (1994). Overexpression of multidrug resistance-associated protein (MRP) increases resistance to natural product drugs. Cancer Res, 54, 357–61
  • Grasberger BL, Lu T, Schubert C, et al. (2005). Discovery and cocrystal structure of benzodiazepinedione HDM2 antagonists that activate p53 in cells. J Med Chem, 48, 909–12
  • Hao YX, He ZW, Zhu JH, et al. (2012). Reversal of multidrug resistance in renal cell carcinoma by short hairpin RNA targeting MDR1 gene. Chin Med J (Engl), 125, 2741–5
  • Hapke G, Yin MB, Rustum YM. (2001). Targeting molecular signals in chk1 pathways as a new approach for overcoming drug resistance. Cancer Metastasis Rev, 20, 109–15
  • Honda R, Tanaka H, Yasuda H. (1997). Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett, 420, 25–7
  • Houghton PJ, Germain GS, Harwood FC, et al. (2004). Imatinib mesylate is a potent inhibitor of the ABCG2 (BCRP) transporter and reverses resistance to topotecan and SN-38 in vitro. Cancer Res, 64, 2333–7
  • Hu W, Kavanagh JJ. (2003). Anticancer therapy targeting the apoptotic pathway. Lancet Oncol, 4, 721–9
  • Kartal-Yandim M, Apohan E, Baran Y. (2013). Therapeutic potential of targeting ceramide/glucosylceramide pathway in cancer. Cancer Chemother Pharmacol, 71, 13–20
  • Kitazono M, Okumura H, Ikeda R, et al. (2001). Reversal of LRP-associated drug resistance in colon carcinoma SW-620 cells. Int J Cancer, 91, 126–31
  • Koblish HK, Zhao S, Franks CF, et al. (2006). Benzodiazepinedione inhibitors of the Hdm2:p53 complex suppress human tumor cell proliferation in vitro and sensitize tumors to doxorubicin in vivo. Mol Cancer Ther, 5, 160–9
  • Kool M, de Haas M, Scheffer GL, et al. (1997). Analysis of expression of cMOAT (MRP2), MRP3, MRP4, and MRP5, homologues of the multidrug resistance-associated protein gene (MRP1), in human cancer cell lines. Cancer Res, 57, 3537–47
  • Krishna R, Mayer LD. (2000). Multidrug resistance (MDR) in cancer mechanisms, reversal using modulators of MDR and the role of MDR modulators in influencing the pharmacokinetics of anticancer drugs. Eur J Pharm Sci, 11, 265–83
  • Kruh GD, Belinsky MG. (2003). The MRP family of drug efflux pumps. Oncogene, 22, 7537–52
  • Kumar A, Kant S, Singh SM. (2013). Targeting monocarboxylate transporter by α-cyano-4-hydroxycinnamate modulates apoptosis and cisplatin resistance of Colo205 cells: implication of altered cell survival regulation. Apoptosis, 18, 1574–85
  • Kunze D, Erdmann K, Froehner M, et al. (2012). siRNA-mediated inhibition of antiapoptotic genes enhances chemotherapy efficacy in bladder cancer cells. Anticancer Res, 32, 4313–18
  • Lamoureux F, Thomas C, Crafter C, et al. (2013). Blocked autophagy using lysosomotropic agents sensitizes resistant prostate tumor cells to the novel Akt inhibitor AZD5363. Clin Cancer Res, 19, 833–44
  • Larsen AK, Escargueil AE, Skladanowski A. (2000). Resistance mechanisms associated with altered intracellular distribution of anticancer agents. Pharmacol Ther, 85, 217–29
  • Larsen AK, Skladanowski A. (1998). Cellular resistance to topoisomerase-targeted drugs: from drug uptake to cell death. Biochem Biophys Acta, 1400, 257–74
  • Laurie NA, Donovan SL, Shih CS, et al. (2006). Inactivation of the p53 pathway in retinoblastoma. Nature, 444, 61–6
  • Leach MO. (1996). Introduction to in vivo MRS of cancer: new perspectives and open problems. Anticancer Res, 16, 1503–14
  • Leonard GD, Fojo T, Bates SE. (2003). The role of ABC transporters in clinical practice. Oncologist, 8, 411–24
  • Li J, Li ZN, Du YJ, et al. (2009). Expression of MRP1, BCRP, LRP, and ERCC1 in advanced non-small-cell lung cancer: correlation with response to chemotherapy and survival. Clin Lung Cancer, 10, 414–21
  • Li K, Chen B, Xu L, et al. (2013). Reversal of multidrug resistance by cisplatin-loaded magnetic Fe3O4 nanoparticles in A549/DDP lung cancer cells in vitro and in vivo. Int J Nanomedicine, 8, 1867–77
  • Liedert B, Materna V, Schadendorf D, et al. (2003). Overexpression of cMOAT (MRP2/ABCC2) is associated with decreased formation of platinum- DNA adducts and decreased G2-arrest in melano.ma cells resistant to cisplatin. J Invest Dermatol, 121, 172–6
  • Lin S, Hoffmann K, Xiao Z, et al. (2013). MEK inhibition induced downregulation of MRP1 and MRP3 expression in experimental hepatocellular carcinoma. Cancer Cell Int, 13, 1–10
  • Liscovitch M, Lavie Y. (2002). Cancer multidrug resistance: a review of recent drug discovery research. IDrugs, 5, 349–55
  • Luqmani YA. (2005). Mechanisms of drug resistance in cancer chemotherapy. Med Princ Pract, 14, 35–48
  • Lv J, Tian Y. (2012). Effect of Src tyrosine kinase inhibition on the drug-resistance as well as MDR1 and LRP expression of the human cis-platinum-resistant lung cancer cell line A549/DDP. Zhongguo Fei Ai Za Zhi, 15, 501–6
  • Maurer BJ, Melton L, Billups C, et al. (2000). Synergistic cytotoxicity in solid tumor cell lines between N-(4-hydroxyphenyl)retinamide and modulators of ceramide metabolism. J Natl Cancer Inst, 92, 1897–909
  • Mechetner EB, Roninson IB. (1992). Efficient inhibition of P-glycoprotein-mediated multidrug resistance with a monoclonal antibody. Proc Natl Acad Sci USA, 89, 5824–8
  • Merchant TE, Meneses P, Gierke LW, et al. (1991). 31P magnetic resonance phospholipid profiles of neoplastic human breast tissues. Br J Cancer, 63, 693–8
  • Merchant TE, de Graaf PW, Minsky BD, et al. (1993). Esophageal cancer phospholipid characterization by 31P NMR. NMR Biomed, 6, 187–93
  • Merchant TE, Diamantis PM, Lauwers G, et al. (1995). Characterization of malignant colon tumors with 31P nuclear magnetic resonance phospholipid and phosphatic metabolite profiles. Cancer, 76, 1715–23
  • Millward MJ, Cantwell BM, Munro NC, et al. (1993). Oral verapamil with chemotherapy for advanced non-small cell lung cancer: a randomised study. Br J Cancer, 67, 1031–5
  • Mulder GJ, Ouwerkerk-Mahadevan S. (1997). Modulation of glutathione conjugation in vivo: how to decrease glutathione conjugation in vivo or in intact cellular systems in vitro. Chem Biol Interact, 105, 17–34
  • Natarajan K, Xie Y, Baer RMT, Ross DR. (2012). Role of breast cancer resistance protein (BCRP/ABCG2) in cancer drug resistance. Biochem Pharmacol, 83, 1084–103
  • Ni Z, Bikadi Z, Rosenberg MF, Mao Q. (2010). Structure and function of the human breast cancer resistance protein (BCRP/ABCG2). Curr Drug Metab, 11, 603–17
  • O’Brien ML, Tew KD. (1996). Glutathione and related enzymes in multidrug resistance. Eur J Cancer, 32, 967–78
  • Ogretmen B, Hannun YA. (2004). Biologically active sphingolipids in cancer pathogenesis and treatment. Nat Rev Cancer, 4, 604–16
  • Ozben T. (2006). Mechanisms and strategies to overcome multiple drug resistance in cancer. FEBS Lett, 580, 2903–9
  • Palaniyandi K, Zhao Q, Chang XB. (2011). Infection of H69AR cells with retroviral particles harboring interfering RNAi significantly reduced the multidrug resistance of these small cell lung cancer cells. Int J Biochem Mol Biol, 2, 155–67
  • Panagiotopoulou V, Richardson G, Jensen OE, Rauch C. (2010). On a biophysical and mathematical model of Pgp-mediated multidrug resistance: understanding the “space-time” dimension of MDR. Eur Biophys J, 39, 201–11
  • Patel J, Mitra AK. (2001). Strategies to overcome simultaneous P-glycoprotein mediated efflux and CYP3A4 mediated metabolism of drugs. Pharmacogenomics, 2, 401–15
  • Pchejetski D, Golzio M, Bonhoure E, et al. (2005). Sphingosine kinase-1 as a chemotherapy sensor in prostate adenocarcinoma cell and mouse models. Cancer Res, 65, 11667–75
  • Pichler A, Zelcer N, Prior JL, et al. (2005). In vivo RNA interference-mediated ablation of MDR1 P-glycoprotein. Clin Cancer Res, 11, 4487–94
  • Pirollo KF, Bouker KB, Chang EH. (2000). Does p53 status influence tumor response to anticancer therapies? Anticancer Drugs, 11, 419–32
  • Pluquet O, Hainaut P. (2001). Genotoxic and non-genotoxic pathways of p53 induction. Cancer Lett, 174, 1–15
  • Ponnusamy S, Meyers-Needham M, Senkal CE, et al. (2010). Sphingolipids and cancer: ceramide and sphingosine-1-phosphate in the regulation of cell death and drug resistance. Future Oncol, 6, 1603–24
  • Prajapati R, Sangamwar AT. (2014). Translocation mechanism of P-glycoprotein and conformational changes occurring at drug-binding site: insights from multi-targeted molecular dynamics. Biochim Biophys Acta, 1838, 2882–98
  • Prinetti A, Millimaggi D, D'Ascenzo S, et al. (2006). Lack of ceramide generation and altered sphingolipid composition are associated with drug resistance in human ovarian carcinoma cells. Biochem J, 395, 311–18
  • Rabindran SK, Ross DD, Doyle LA, et al. (2000). Fumitremorgin C reverses multidrug resistance in cells transfected with the breast cancer resistance protein. Cancer Res, 60, 47–50
  • Radin NS. (2002). The development of aggressive cancer: a possible role for sphingolipids. Cancer Invest, 20, 779–86
  • Rauch C. (2009). Toward a mechanical control of drug delivery. On the relationship between Lipinski's 2nd rule and cytosolic pH changes in doxorubicin resistance levels in cancer cells: a comparison to published data, Eur Biophys J, 38, 829–46
  • Rauch C, Pluen A. (2007). Multi drug resistance-dependent “vacuum cleaner” functionality potentially driven by the interactions between endocytosis, drug size and Pgp-like transporters surface density, Eur Biophys J, 36, 121–31
  • Reed JC. (1995). Bcl-2: prevention of apoptosis as a mechanism of drug resistance. Hematol Oncol Clin North Am, 9, 451–73
  • Riordan JR, Ling V. (1979). Purification of P-glycoprotein from plasma membrane vesicles of Chinese hamster ovary cell mutants with reduced colchicine permeability. J Biol Chem, 254, 12701–5
  • Rooswinkel RW, van de Kooij B, Verheij M, Borst J. (2012). Bcl-2 is a better ABT-737 target than Bcl-xL or Bcl-w and only Noxa overcomes resistance mediated by Mcl-1, Bfl-1, or Bcl-B. Cell Death Dis, 3, e366
  • Saito G, Swanson JA, Lee KD. (2003). Drug delivery strategy utilizing conjugation via reversible disulfide linkages: role and site of cellular reducing activities. Adv Drug Deliv Rev, 55, 199–215
  • Sancar A, Lindsey-Boltz LA, Unsal-Kacmaz K, Linn S. (2004). Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem, 73, 39–85
  • Sarkadi B, Müller M. (1997). Search for specific inhibitors of multidrug resistance in cancer. Sem Cancer Biol, 8, 171–82
  • Schisselbauer JC, Silber R, Papadopoulos E, et al. (1990). Characterization of glutathione S-transferase expression in lymphocytes from chronic lymphocytic leukemia patients. Cancer Res, 50, 3562–68
  • Shah MA, Schwartz GK. (2001). Cell cycle-mediated drug resistance: an emerging concept in cancer therapy. Clin Cancer Res, 7, 2168–81
  • Sharom FJ, Yu X, Lu P, et al. (1999). Interaction of the P-glycoprotein multidrug transporter (MDR1) with high affinity peptide chemosensitizers in isolated membranes, reconstituted systems, and intact cells. Biochem Pharmacol, 58, 571–86
  • Sherbakova EA, Stromskaia TP, Rybalkina EIU, et al. (2008). Role of PTEN protein in multidrug resistance of prostate cancer cells. Mol Biol, 42, 487–93
  • Simon S, Roy D, Schindler M. (1994). Intracellular pH and the control of multidrugresistance. Proc Natl Acad Sci USA, 91, 1128–32
  • Smith ML, Seo YR. (2002). p53 regulation of DNA excision repair pathways. Mutagenesis, 17, 149–56
  • Stambolic V, Suzuki A, de la Pompa JL, et al. (1998). Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell, 95, 29–39
  • Stavrovskaya AA. (2000). Cellular mechanisms of multidrug resistance of tumor cells. Biochemistry, 65, 95–106
  • Sun SH, Zheng M, Ding K, et al. (2008). A small molecule that disrupts Mdm2-p53 binding activates p53, induces apoptosis, and sensitizes lung cancer cells to chemotherapy. Cancer Biol Ther, 7, 845–52
  • Szakács G, Paterson JK, Ludwig JA, et al. (2006). Targeting multidrug resistance in cancer. Nat Rev, 3, 219–34
  • Szakács G, Annereau JP, Lababidi S, et al. (2004). Predicting drug sensitivity and resistance: profiling ABC transporter genes in cancer cells. Cancer Cell, 6, 129–37
  • Tew KD. (1994). Glutathione-associated enzymes in anticancer drug resistance. Cancer Res, 54, 4313–20
  • Veldman RJ, Mita A, Cuvillier O, et al. (2003). The absence of functional glucosylceramide synthase does not sensitize melanoma cells for anticancer drugs. FASEB J, 17, 1144–6
  • Visentin B, Vekich JA, Sibbald BJ, et al. (2006). Validation of an anti-sphingosine-1-phosphate antibody as a potential therapeutic in reducing growth, invasion, and angiogenesis in multiple tumor lineages. Cancer Cell, 9, 225–38
  • Walworth NC, Bernards R. (1996). Rad-dependent response of the chk1-encoded protein kinase at the DNA damage checkpoint. Science, 271, 353–6
  • Wang F, Li T, Zhang B, et al. (2013). MicroRNA-19a/b regulates multidrug resistance in human gastric cancer cells by targeting PTEN. Biochem Biophys Res Commun, 434, 688–94
  • Wang W, Rastinejad F, El-Deiry WS. (2003). Restoring p53-dependent tumor suppression. Cancer Biol Ther, 2, S55–63
  • Wang Z, Sun Y. (2010). Targeting p53 for novel anticancer therapy. Transl Oncol, 3, 1–12
  • Xian XS, Park H, Choi MG, Park JM. (2013). Cannabinoid receptor agonist as an alternative drug in 5-fluorouracil-resistant gastric cancer cells. Anticancer Res, 33, 2541–7
  • Xiao Z, Chen Z, Gunasekera AH, et al. (2003). Chk1 mediates S and G2 arrests through Cdc25A degradation in response to DNA-damaging agents. J Biol Chem, 278, 21767–73
  • Yan XU, Feng ZHI, Guangming XU, et al. (2012). Overcoming multidrug-resistance in vitro and in vivo using the novel P-glycoprotein inhibitor 1416. Biosci Rep, 32, 559–66
  • Yu HG, Ai YW, Yu LL, et al. (2008). Phosphoinositide 3-kinase/Akt pathway plays an important role in chemoresistance of gastric cancer cells against etoposide and doxorubicin induced cell death. Int J Cancer, 122, 433–43
  • Yu M, Ocana A, Tannock IF. (2013). Reversal of ATP-binding cassette drug transporter activity to modulate chemoresistance: why has it failed to provide clinical benefit? Cancer Metastasis Rev, 32, 211–27
  • Zhao BX, Sun YB, Wang SQ, et al. (2013). Grape seed procyanidin reversal of P-glycoprotein associated multi-drug resistance via down-regulation of NF-κb and MAPK/ERK mediated YB-1 activity in A2780/T cells. PLoS One, 8, e71071
  • Zhao Y, Yu L, Lou F, et al. (1999). The clinical significance of lung resistance-related protein gene (lrp), multidrug resistance-associated protein gene (mrp) and mdr-1/p170 expression in acute leukemia. Zhonghua Nei Ke Za Zhi, 38, 760–3
  • Zhu W, Shan X, Wang T, et al. (2010). miR-181b modulates multidrug resistance by targeting BCL2 in human cancer cell lines. Int J Cancer, 127, 2520–9
  • Zhu W, Zhu D, Lu S, et al. (2012). miR-497 modulates multidrug resistance of human cancer cell lines by targeting BCL2. Med Oncol, 29, 384–91

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.