Role of ABC transporters in cancer chemotherapy

Sun, Yulin; Patel, Atish; Kumar, Priyank; Chen, Zhe‐Sheng

doi:10.5732/cjc.011.10466

Cited by 109 publications

(73 citation statements)

References 68 publications

(81 reference statements)

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“…Multidrug resistance in cancer can significantly hamper the response to chemotherapy and increase the likelihood of mortality 1, 2 .…”

Section: Introductionmentioning

confidence: 99%

“…Multidrug resistance occurs when cancer cells exposed to one anticancer drug show cross-resistance to various anticancer drugs that are structurally and functionally different 1 . Intrinsic and acquired MDR has long been recognized as causes of chemotherapeutic failure 3 .…”

Section: Introductionmentioning

confidence: 99%

“…Expression of primary active (energy-dependent) ATP-binding cassette (ABC) efflux pumps has been linked to tumor aggressiveness in different tumor types as the drugs are carefully channeled across the biological membrane 1 . ABC transporters are highly expressed in pharmacologically important tissues and translocate a wide variety of solutes across biological membranes 1 .…”

Section: Introductionmentioning

confidence: 99%

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Kakarla

Inupakutika

Devireddy

et al. 2016

IJPSR

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One of the major obstacles to the successful chemotherapy towards several cancers is multidrug resistance of human cancer cells to anti-cancer drugs. An important contributor to multidrug resistance is the human multidrug resistance protein-1 transporter (MRP1), which is an efflux pump of the ABC (ATP binding cassette) superfamily. Thus, highly efficacious, third generation MRP1 inhibitors, like tariquidar analogues, are promising inhibitors of multidrug resistance and are under clinical trials. To maximize the efficacy of MRP1 inhibitors and to reduce systemic toxicity, it is important to limit the exposure of MRP1 inhibitors and anticancer drugs to normal tissues and to increase their co-localization with tumor cells. Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) associated with 3D-Quantitiative structure-activity relationship (3D-QSAR) studies were performed on a series of tariquidar analogues, as selective MDR modulators. Best predictability was obtained with CoMFA model r2(non-cross-validated square of correlation coefficient) = 0.968, F value = 151.768 with five components, standard error of estimate = 0.107 while the CoMSIA yielded r2 = 0.982, F value = 60.628 with six components, and standard error of estimate = 0.154. These results indicate that steric, electrostatic, hydrophobic (lipophilic), and hydrogen bond donor substituents play significant roles in multidrug resistance modulation of tariquidar analogues upon MRP1. The tariquidar analogue and MRP1 binding and stability data generated from CoMFA and CoMSIA based 3D–contour maps may further aid in study and design of tariquidar analogues as novel, potent and selective MDR modulator drug candidates.

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“…Multidrug resistance in cancer can significantly hamper the response to chemotherapy and increase the likelihood of mortality 1, 2 .…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Untitled

Kakarla

Inupakutika

Devireddy

et al. 2016

IJPSR

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“…Human P-gp, a 170 kDa trans-membrane glycoprotein, is composed of 12 hydrophobic domains and two nucleotide domains [ 220 ], and is a major component of the blood brain barrier [ 221 ]. It can transport several small molecules, either from the cytosol or from the cell membrane, out of the cell, which signifi cantly reduces cellular accumulation of cytotoxic molecules [ 138 , 222 ].…”

Section: Atp-binding Cassettementioning

confidence: 99%

Nanomedicine: The Promise and Challenges in Cancer Chemotherapy

Naguib

Cui

2014

Advances in Experimental Medicine and Biology

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“…Decreasing ABCB1 expression and increasing ABC C1 e xp re ss io n we re a ss o c ia te d wi th i nc re as in g dedifferentiation and microvascular invasion 11,12) . Mitoxantrone, boron-dipyrromethene (BODIPY)-prazosin and almost all nucleoside inhibitors are substrates of ABCG2 13,14) . As a progenitor marker, ABCG2 was also used to identify the cancer stem cells (CSCs) of HCC 15) .Although several ABC transporters have been confirmed abnormally expression in HCC tissue 16) , there is discrepancy between studies aimed at the modulation of ABC transporters in HCC.…”

Section: Introductionmentioning

confidence: 99%

Clinical Significance of ABC Transporter Expression in Patients with Hepatocellular Carcinoma

Fan

Zhang²,

Zhang

et al. 2016

J. Hard Tissue Biology.

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To gain insight into the clinical significance of expression of ABC transporter antigen in patients with hepatocellular carcinoma (HCC), we used immunohistochemistry to determine the patterns of ABCB1, ABCC1 and ABCG2 expression in 30 resected HCC tissues, 26 paired adjacent nonneoplastic tissues and 9 cirrhosis tissues accompanied with chronic hepatitis B virus infection in this study. It was found that the expression rates of ABCB1, ABCC1 and ABCG2 were 56.7 %, 93.3 % and 83.3 % in patients with HCC, respectively. ABCB1 and ABCC1 were expressed significantly differently among HCC, adjacent non-neoplastic and cirrhosis tissues. There were no significant differences in the clinical factors associated with the expression of these three ABC transporter antigens. Furthermore, preoperative TACE treatment didn't affect the expression of these three ABC transporters. Moreover, patients with higher expression of both ABCC1 and ABCB1 showed significantly shorter disease-free survival (DFS) than those with lower expression of both antigens (P<0.01).Therefore, higher expression of ABCC1 and ABCB1 might be an unfavorable prognostic factor in patients of HCC, and represent an important hurdle to chemotherapy.

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Role of ABC transporters in cancer chemotherapy

Cited by 109 publications

References 68 publications

Untitled

Untitled

Nanomedicine: The Promise and Challenges in Cancer Chemotherapy

Clinical Significance of ABC Transporter Expression in Patients with Hepatocellular Carcinoma

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