scholarly journals Comparative Study of the Sensitivities of Cancer Cells to Doxorubicin, and Relationships between the Effect of the Drug-Efflux Pump P-gp

2014 ◽  
Vol 37 (12) ◽  
pp. 1926-1935 ◽  
Author(s):  
Golam Kibria ◽  
Hiroto Hatakeyama ◽  
Kosuke Akiyama ◽  
Kyoko Hida ◽  
Hideyoshi Harashima
Keyword(s):  
Comparative Study ◽  
Cancer Cells ◽  
Efflux Pump ◽  
Drug Efflux ◽  
Drug Efflux Pump

Human hepatocellular carcinoma cell lines exhibit multidrug resistance unrelated to MRD1 gene expression

1991 ◽  
Vol 98 (3) ◽  
pp. 317-322
Author(s):  
D.W. Shen ◽  
Y.G. Lu ◽  
K.V. Chin ◽  
I. Pastan ◽  
M.M. Gottesman
Keyword(s):  
Hepatocellular Carcinoma ◽  
Multidrug Resistance ◽  
Cancer Cells ◽  
Cell Lines ◽  
Actinomycin D ◽  
Efflux Pump ◽  
Mdr1 Gene ◽  
Drug Efflux ◽  
P Glycoprotein ◽  
Drug Efflux Pump

Multidrug resistance of human cancer cells may result from expression of P-glycoprotein, the product of the MRD1 gene, acting as an energy-dependent drug efflux pump. However, direct evidence that expression of the MDR1 gene contributes to the multidrug resistance of human liver carcinomas has not been established. In this study, we tested five cell lines derived from human hepatocellular carcinomas for sensitivity to a variety of drugs used widely as anticancer agents; these included vinblastine, doxorubicin, actinomycin D, mitomycin C, 5-fluorouracil, 6-mercaptopurine, melphalan, methotrexate, cis-platinum and etoposide (VP-16). All five hepatoma cell lines were resistant at different levels to these chemicals compared to human KB cells. Although it has been demonstrated that resistance to vinblastine, colchicine, doxorubicin and actinomycin D in human multidrug-resistant cells is associated with overexpression of P-glycoprotein, very little expression of P-glycoprotein was found in these human hepatoma cells. Neither verapamil nor quinidine, inhibitors of the drug efflux pump, were able to overcome multidrug resistance in hepatoma cells. These results indicate that the multidrug resistance phenotype in human hepatocellular carcinoma cells cannot be attributed to expression of the MDR1 gene, but that novel mechanisms may account for the resistance of these cancer cells.

scholarly journals MDR1 Drug Efflux Pump Promotes Intrinsic and Acquired Resistance to PROTACs in Cancer Cells

2021 ◽  
Author(s):  
Alison M. Kurimchak ◽  
Carlos Herrera-Montávez ◽  
Sara Montserrat ◽  
Daniela Araiza ◽  
Jianping Hu ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Efflux Pump ◽  
Acquired Resistance ◽  
Drug Efflux ◽  
Cancer Therapies ◽  
Erbb Receptor ◽  
Intrinsic Resistance ◽  
Colorectal Cancer Cells ◽  
Drug Efflux Pump ◽  
Potent Drug

ABSTRACTPROTACs (Proteolysis-Targeting Chimeras) represent a promising new class of drugs that selectively degrade proteins of interest from cells. PROTACs targeting oncogenes are avidly being explored for cancer therapies, with several currently in clinical trials. Drug resistance represents a significant challenge in cancer therapies, and the mechanism by which cancer cells acquire resistance to PROTACs remains poorly understood. Using proteomics, we discovered acquired and intrinsic resistance to PROTACs in cancer cells can be mediated by upregulation of the drug efflux pump MDR1. PROTAC-resistant cells could be re-sensitized to PROTACs through co-administering MDR1 inhibitors. Notably, co-treatment of MDR1-overexpressing colorectal cancer cells with MEK1/2 or KRASG12C degraders and the dual ErbB receptor/MDR1 inhibitor lapatinib exhibited potent drug synergy due to simultaneous blockade of MDR1 and ErbB receptor activity. Together, our findings suggest that concurrent blockade of MDR1 will likely be required in combination with PROTACs to achieve durable protein degradation and therapeutic response in cancer.

P-glycoprotein as the drug efflux pump in primary cultured bovine brain capillary endothelial cells

Life Sciences ◽  
1992 ◽  
Vol 51 (18) ◽  
pp. 1427-1437 ◽  
Author(s):  
Akira Tsuji ◽  
Tetsuya Terasaki ◽  
Yasushi Takabatake ◽  
Yoshiyuki Tenda ◽  
Ikumi Tamai ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Efflux Pump ◽  
Bovine Brain ◽  
Drug Efflux ◽  
Brain Capillary ◽  
Brain Capillary Endothelial Cells ◽  
P Glycoprotein ◽  
Capillary Endothelial Cells ◽  
Drug Efflux Pump

Structure-property correlation in gallic acid and 4-cyanopyridine cocrystal and binding studies with drug efflux pump in bacteria

2021 ◽  
Vol 1225 ◽  
pp. 129279
Author(s):  
Shyam Goswami ◽  
Arabinda Ghosh ◽  
Karmajyoti Borah ◽  
Anupam Mahanta ◽  
Ankur K Guha ◽  
...  
Keyword(s):  
Gallic Acid ◽  
Efflux Pump ◽  
Drug Efflux ◽  
Structure Property ◽  
Binding Studies ◽  
Property Correlation ◽  
Drug Efflux Pump

scholarly journals Phytochemicals increase the antibacterial activity of antibiotics by acting on a drug efflux pump

2014 ◽  
Vol 3 (6) ◽  
pp. 885-896 ◽  
Author(s):  
Thelma Ohene‐Agyei ◽  
Rumana Mowla ◽  
Taufiq Rahman ◽  
Henrietta Venter
Keyword(s):  
Antibacterial Activity ◽  
Efflux Pump ◽  
Drug Efflux ◽  
Drug Efflux Pump

SMAR1 repression by pluripotency factors and consequent chemoresistance in breast cancer stem-like cells is reversed by aspirin

2020 ◽  
Vol 13 (654) ◽  
pp. eaay6077
Author(s):  
Apoorva Bhattacharya ◽  
Shravanti Mukherjee ◽  
Poulami Khan ◽  
Shruti Banerjee ◽  
Apratim Dutta ◽  
...  
Keyword(s):  
Efflux Pump ◽  
Chemotherapy Resistance ◽  
Cooperative Interaction ◽  
Drug Efflux ◽  
Cancer Stemness ◽  
Gene Encoding ◽  
Pluripotency Factors ◽  
Tumor Bearing ◽  
Drug Efflux Pumps ◽  
Drug Efflux Pump

The high abundance of drug efflux pumps in cancer stem cells (CSCs) contributes to chemotherapy resistance. The transcriptional regulator SMAR1 suppresses CSC expansion in colorectal cancer, and increased abundance of SMAR1 is associated with better prognosis. Here, we found in breast tumors that the expression of SMAR1 was decreased in CSCs through the cooperative interaction of the pluripotency factors Oct4 and Sox2 with the histone deacetylase HDAC1. Overexpressing SMAR1 sensitized CSCs to chemotherapy through SMAR1-dependent recruitment of HDAC2 to the promoter of the gene encoding the drug efflux pump ABCG2. Treating cultured CSCs or 4T1 tumor-bearing mice with the nonsteroidal anti-inflammatory drug aspirin restored SMAR1 expression and ABCG2 repression and enhanced tumor sensitivity to doxorubicin. Our findings reveal transcriptional mechanisms regulating SMAR1 that also regulate cancer stemness and chemoresistance and suggest that, by restoring SMAR1 expression, aspirin might enhance chemotherapeutic efficacy in patients with stem-like tumors.

scholarly journals Identification and Evolution of Drug Efflux Pump in Clinical Enterobacter aerogenes Strains Isolated in 1995 and 2003

PLoS ONE ◽  
2008 ◽  
Vol 3 (9) ◽  
pp. e3203 ◽  
Author(s):  
Jacqueline Chevalier ◽  
Céline Mulfinger ◽  
Eric Garnotel ◽  
Pierre Nicolas ◽  
Anne Davin-Régli ◽  
...  
Keyword(s):  
Efflux Pump ◽  
Enterobacter Aerogenes ◽  
Drug Efflux ◽  
Drug Efflux Pump

scholarly journals The synergistic role of ATP-dependent drug efflux pump and focal adhesion signaling pathways in vinorelbine resistance in lung cancer

2018 ◽  
Vol 7 (2) ◽  
pp. 408-419 ◽  
Author(s):  
Takao Nakanishi ◽  
Toshi Menju ◽  
Shigeto Nishikawa ◽  
Koji Takahashi ◽  
Ryo Miyata ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Signaling Pathways ◽  
Focal Adhesion ◽  
Efflux Pump ◽  
Drug Efflux ◽  
Drug Efflux Pump

Modeling of P-glycoprotein-involved epithelial drug transport in MDCK cells

1999 ◽  
Vol 277 (1) ◽  
pp. F84-F96 ◽  
Author(s):  
Shinya Ito ◽  
Cindy Woodland ◽  
Balázs Sarkadi ◽  
Guido Hockmann ◽  
Scott E. Walker ◽  
...  
Keyword(s):  
Drug Transport ◽  
Diffusion Processes ◽  
Efflux Pump ◽  
Mdck Cells ◽  
Basolateral Membrane ◽  
Drug Efflux ◽  
Drug Transfer ◽  
P Glycoprotein ◽  
Drug Efflux Pump ◽  
Apical Membranes

P-glycoprotein (P-gp) on the apical membranes of epithelial cells is known as a drug efflux pump. However, unclear is its integral quantitative role in the overall epithelial drug transfer, which also involves distinct diffusion processes in parallel and sequence. We used a simple three-compartment model to obtain kinetic parameters of each drug transfer mechanism, which can quantitatively describe the transport time courses of P-gp substrates, digoxin and vinblastine, across P-gp-expressing MDCK cell monolayers grown on permeable filters. Our results show that the model, which assumes a functionally single drug efflux pump in the apical membrane with diffusion across two membranes and intercellular junctions, is the least complex model with which to quantitatively reproduce the characteristics of the data. Interestingly, the model predicts that the MDCK apical membranes are less diffusion permeable than the basolateral membrane for both drugs and that the distribution volume of vinblastine is 10-fold higher than that of digoxin. Additional experiments verified these model predictions. The modeling approach is feasible to quantitatively describe overall kinetic picture of epithelial drug transport. Further model refinement is necessary to incorporate other modes of drug transport such as transcytosis. Also, whether P-gp solely accounts for the pump function in this model awaits more studies.

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