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WHI-P154 enhances the chemotherapeutic effect of anticancer agents in ABCG2-overexpressing cells.

Zhang H, Zhang YK, Wang YJ, Kathawala RJ, Patel A, Zhu H, Sodani K, Talele TT, Ambudkar SV, Chen ZS, Fu LW - Cancer Sci. (2014)

Bottom Line: We found that WHI-P154 significantly enhanced the sensitivity of ABCG2-overexpressing cells to its substrates.WHI-P154 moderately sensitized ABCB1-overexpressing KB-C2 cells to its substrates whereas showed no sensitizing effect on ABCC1-, ABCC2 or ABCC10-mediated drug resistance.Collectively, these findings highlighted WHI-P154 could significantly reverse ABCG2-mediated multidrug drug resistance by directly blocking the efflux function.

View Article: PubMed Central - PubMed

Affiliation: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St John's University, Queens, New York, USA.

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Effect of WHI-P154 on the ATPase activity of ABCG2. Crude membranes (10–20 μg protein/reaction) from High-five cells expressing ABCG2 were incubated with increasing concentrations of WHI-P154 (0–50 μM), in the presence and absence of 10 mM vanadate, in ATPase assay buffer as described in Materials and Methods. The mean values are plotted and error bars depict SD (n = 3).
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fig04: Effect of WHI-P154 on the ATPase activity of ABCG2. Crude membranes (10–20 μg protein/reaction) from High-five cells expressing ABCG2 were incubated with increasing concentrations of WHI-P154 (0–50 μM), in the presence and absence of 10 mM vanadate, in ATPase assay buffer as described in Materials and Methods. The mean values are plotted and error bars depict SD (n = 3).

Mentions: The drug efflux function of ABCG2 is coupled with ATP hydrolysis, which is stimulated in the presence of ABCG2 substrates. To assess the effect of WHI-P154 on the ATPase activity of ABCG2, the membrane vesicles of High Five insect cells overexpressing ABCG2 were used in the presence of various concentrations of WHI-P154 under conditions that suppressed the activity of other major membrane ATPases. As shown in Figure 4, WHI-P154 produced a significantly stimulation of ABCG2 ATPase activity at low concentrations (<10 μM). The results suggested that WHI-P54 may be a substrate for ABCG2.


WHI-P154 enhances the chemotherapeutic effect of anticancer agents in ABCG2-overexpressing cells.

Zhang H, Zhang YK, Wang YJ, Kathawala RJ, Patel A, Zhu H, Sodani K, Talele TT, Ambudkar SV, Chen ZS, Fu LW - Cancer Sci. (2014)

Effect of WHI-P154 on the ATPase activity of ABCG2. Crude membranes (10–20 μg protein/reaction) from High-five cells expressing ABCG2 were incubated with increasing concentrations of WHI-P154 (0–50 μM), in the presence and absence of 10 mM vanadate, in ATPase assay buffer as described in Materials and Methods. The mean values are plotted and error bars depict SD (n = 3).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317847&req=5

fig04: Effect of WHI-P154 on the ATPase activity of ABCG2. Crude membranes (10–20 μg protein/reaction) from High-five cells expressing ABCG2 were incubated with increasing concentrations of WHI-P154 (0–50 μM), in the presence and absence of 10 mM vanadate, in ATPase assay buffer as described in Materials and Methods. The mean values are plotted and error bars depict SD (n = 3).
Mentions: The drug efflux function of ABCG2 is coupled with ATP hydrolysis, which is stimulated in the presence of ABCG2 substrates. To assess the effect of WHI-P154 on the ATPase activity of ABCG2, the membrane vesicles of High Five insect cells overexpressing ABCG2 were used in the presence of various concentrations of WHI-P154 under conditions that suppressed the activity of other major membrane ATPases. As shown in Figure 4, WHI-P154 produced a significantly stimulation of ABCG2 ATPase activity at low concentrations (<10 μM). The results suggested that WHI-P54 may be a substrate for ABCG2.

Bottom Line: We found that WHI-P154 significantly enhanced the sensitivity of ABCG2-overexpressing cells to its substrates.WHI-P154 moderately sensitized ABCB1-overexpressing KB-C2 cells to its substrates whereas showed no sensitizing effect on ABCC1-, ABCC2 or ABCC10-mediated drug resistance.Collectively, these findings highlighted WHI-P154 could significantly reverse ABCG2-mediated multidrug drug resistance by directly blocking the efflux function.

View Article: PubMed Central - PubMed

Affiliation: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St John's University, Queens, New York, USA.

Show MeSH
Related in: MedlinePlus