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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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Cytotoxicity of WHI-P154 in the drug-resistant and parental sensitive cells. The chemical structure of WHI-P154 (a), MTT cytotoxicity assay was assessed in KB-3-1 and KB-C2 cells (b), H460 and H460/MX20 cells (c), HEK293/pcDNA3.1 and ABCG2 transfected cells (d), HEK293/pcDNA3.1 and HEK293/ABCC1 cells (e), HEK293/pcDNA3.1 and HEK293/ABCC10 cells (f), LLC/CMV and LLC/cMOAT cells (g). All the cells were exposed to various concentrations of WHI-P154 for 72 h. Each point represents the mean ± standard deviations (SDs) for three determinations. Each experiment was performed in three replicate wells.
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fig01: Cytotoxicity of WHI-P154 in the drug-resistant and parental sensitive cells. The chemical structure of WHI-P154 (a), MTT cytotoxicity assay was assessed in KB-3-1 and KB-C2 cells (b), H460 and H460/MX20 cells (c), HEK293/pcDNA3.1 and ABCG2 transfected cells (d), HEK293/pcDNA3.1 and HEK293/ABCC1 cells (e), HEK293/pcDNA3.1 and HEK293/ABCC10 cells (f), LLC/CMV and LLC/cMOAT cells (g). All the cells were exposed to various concentrations of WHI-P154 for 72 h. Each point represents the mean ± standard deviations (SDs) for three determinations. Each experiment was performed in three replicate wells.

Mentions: We investigated the cytotoxicity of WHI-P154 in different cells by MTT assay. As shown in Figure 1, approximately 85% of the cells survived at the concentration of 4 μM WHI-P154 (Fig. 1b–g). Therefore, WHI-P154 at a concentration of 4 μM was chosen as a maximum concentration for combination treatment with known ABCB1, ABCG2, ABCC1, ABCC2 or ABCC10 substrate anticancer drugs.


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)

Cytotoxicity of WHI-P154 in the drug-resistant and parental sensitive cells. The chemical structure of WHI-P154 (a), MTT cytotoxicity assay was assessed in KB-3-1 and KB-C2 cells (b), H460 and H460/MX20 cells (c), HEK293/pcDNA3.1 and ABCG2 transfected cells (d), HEK293/pcDNA3.1 and HEK293/ABCC1 cells (e), HEK293/pcDNA3.1 and HEK293/ABCC10 cells (f), LLC/CMV and LLC/cMOAT cells (g). All the cells were exposed to various concentrations of WHI-P154 for 72 h. Each point represents the mean ± standard deviations (SDs) for three determinations. Each experiment was performed in three replicate wells.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig01: Cytotoxicity of WHI-P154 in the drug-resistant and parental sensitive cells. The chemical structure of WHI-P154 (a), MTT cytotoxicity assay was assessed in KB-3-1 and KB-C2 cells (b), H460 and H460/MX20 cells (c), HEK293/pcDNA3.1 and ABCG2 transfected cells (d), HEK293/pcDNA3.1 and HEK293/ABCC1 cells (e), HEK293/pcDNA3.1 and HEK293/ABCC10 cells (f), LLC/CMV and LLC/cMOAT cells (g). All the cells were exposed to various concentrations of WHI-P154 for 72 h. Each point represents the mean ± standard deviations (SDs) for three determinations. Each experiment was performed in three replicate wells.
Mentions: We investigated the cytotoxicity of WHI-P154 in different cells by MTT assay. As shown in Figure 1, approximately 85% of the cells survived at the concentration of 4 μM WHI-P154 (Fig. 1b–g). Therefore, WHI-P154 at a concentration of 4 μM was chosen as a maximum concentration for combination treatment with known ABCB1, ABCG2, ABCC1, ABCC2 or ABCC10 substrate anticancer drugs.

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