The ability of verapamil to restore intracellular accumulation of anthracyclines in multidrug resistant cells depends on the kinetics of their uptake

Mankhetkorn, Samlee; Garnier‐Suillerot, Arlette

doi:10.1016/s0014-2999(97)01548-3

Cited by 36 publications

(27 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…were incubated in the presence of 10 mM CsA, confirming that this concentration of CsA fully inhibits P-gp activity (Mankhetkorn and Garnier-Suillerot, 1998). Importantly, following P-gp inhibition DOX became cytostatic in K562 R cells (not shown) but did not induced cell death (Figure 6b), indicating that other mechanisms of resistance exist in the studied clone.…”

Section: Mitochondria In Dox-resistant Cells F De Oliveira Et Almentioning

confidence: 55%

Effects of permeability transition inhibition and decrease in cytochrome c content on doxorubicin toxicity in K562 cells

Oliveira

Chauvin

Ronot³

et al. 2005

Oncogene

View full text Add to dashboard Cite

As mitochondria play a key role in the commitment to cell death, we have investigated the mitochondrial consequences of resistance to doxorubicin (DOX) in K562 cells. We found that the permeability transition pore (PTP) inhibitor cyclosporine A (CsA) failed to inhibit PTP opening in the resistant clone. Moreover, the Ca 2 þ loading capacity in the resistant clone was identical to that observed in the parent cells in the presence of CsA, suggesting that the PTP was already inhibited in a CsAlike manner in the resistant cells. In agreement with this proposal, the mitochondrial target of CsA cyclophilin D (CyD) decreased by half in the resistant cells. The levels of adenine nucleotide translocator, voltage anion-dependent channel, Bax, Bcl-2, Bcl-x L , AIF and Smac/Diablo, were similar in both cell lines, whereas cytochrome c content was divided by three in the resistant cells. Since P-glycoprotein inhibition did not restore DOX toxicity in the resistant cells, while DOX-induced cell death in the parent cells was prevented by either PTP inhibition or siRNA-induced decrease in cytochrome c content, we conclude that the inhibition of PTP opening and the decrease in cytochrome c content participate in the mechanism that makes K562 cells resistant to DOX.

show abstract

Section: Mitochondria In Dox-resistant Cells F De Oliveira Et Almentioning

confidence: 55%

Effects of permeability transition inhibition and decrease in cytochrome c content on doxorubicin toxicity in K562 cells

Oliveira

Chauvin

Ronot³

et al. 2005

Oncogene

View full text Add to dashboard Cite

show abstract

“…The uptake of pirarubicin in cells was followed by monitoring the decrease in the fluorescence signal at 590 nm (l ex ¼ 480 nm) according to the previously described method [46].…”

Section: Cellular Drug Accumulation and Mtt Assaymentioning

confidence: 99%

Multidrug resistance (MDR) reversers: High activity and efficacy in a series of asymmetrical N,N-bis(alkanol)amine aryl esters

Dei

Coronnello

Floriddia

et al. 2014

European Journal of Medicinal Chemistry

View full text Add to dashboard Cite

“…Since we have previously demonstrated that the intracellular MDR transporters were also found localized on the intracellular organelle membrane and they also play important role on pumping the drugs from cytosol into these organelles for example in SiHa cells (Laochariyakul et al, 2003;Mankhetkorn and Garnier-Suillerot, 1998;Dechsupa and Mankhetkorn, 2009). In this study we preliminary determined that for K562/adr and GLC4/adr cells, the functional P-glycoprotein and MRP1 protein was localized on the plasma membrane (GarnierSuillerot et al, 2001).…”

Section: Discussionmentioning

confidence: 62%

“…Quercetin, quercetrin and rutin enhanced cytotoxicity of pirarubicin against K562/adr and GLC4/adr cells: The potential MDR reversing action of flavonoids was primarily studied by using the cotreatment of anticancer drug, pirarubicin or daunorubicin and quercetin, quercetrin or rutin compared with the series of co-treatment of pirarubicin or daunorubicin and the known inhibitor of MDR protein transporters (cyclosporine A or verapamil) (Mankhetkorn and Garnier-Suillerot, 1998).…”

Section: Cytotoxicity Of Quercetin Quercetrin and Rutinmentioning

confidence: 99%

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

Choiprasert¹

2010

American Journal of Pharmacology and Toxicology

View full text Add to dashboard Cite

Problem statement: Quercetin and its glycoside derivatives are increasingly receiving interests as new generation of anticancer molecules and were recognized by multidrug resistant transporters such as P-glycoprotein and MRP1 protein. Of relevance to their use as anticancer agents alone or in combination with other agents, this study aims to analyze the interaction of the compounds with the MDR transporters including P-glycoprotein and MRP1 protein in living multidrug resistant cells. Approach: The potential MDR reversing action of flavonoids was assessed by using the cotreatment of anticancer drug, pirarubicin or daunorubicin and quercetin, quercetrin or rutin compared with the series of co-treatment of pirarubicin or daunorubicin and the known inhibitor such as cyclosporine A and verapamil. The evidence of direct interaction of molecules with MDR protein was investigated by measuring the ability of inhibition of the rate of P-glycoprotein-and MRP1-mediated efflux of pirarubicin out of cells. Results: Quercetin and its glycoside derivatives efficiently inhibited cancer cell proliferation and re-sensitize the MDR cells to pirarubicin but not for daunorubicin. Our results clearly show that quercetin, quercetrin except rutin non-competitively inhibited the function of P-glycoprotein in K562/adr and MRP1 in GLC4/adr cells. The determined K I value of P-glycoprotein was equal to 0.33 µM for quercetin and 1 µM for quercetrin and K I value of MRP1 was equal to 0.45 µM for quercetin and 0.5 µM for quercetrin. Conclusion: The overall results demonstrated that quercetin, quercetrin and rutin should be considered as potential pharmaceutical molecules that might be used as MDR inhibitors.

show abstract

The ability of verapamil to restore intracellular accumulation of anthracyclines in multidrug resistant cells depends on the kinetics of their uptake

Cited by 36 publications

References 25 publications

Effects of permeability transition inhibition and decrease in cytochrome c content on doxorubicin toxicity in K562 cells

Effects of permeability transition inhibition and decrease in cytochrome c content on doxorubicin toxicity in K562 cells

Multidrug resistance (MDR) reversers: High activity and efficacy in a series of asymmetrical N,N-bis(alkanol)amine aryl esters

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

Contact Info

Product

Resources

About