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- W2148736073 abstract "Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DCBackground: Stemofoline is a plant alkaloid isolated form Stemona, which is native to southeastern Asia. P-glycoprotein (Pgp), a member of the ATP-binding cassette (ABC) transporter superfamily is implicated in multidrug resistance (MDR) in cancer cells. Aim: To investigate the effect of stemofoline on Pgp function.Methods and Results: Stemofoline stimulated Pgp-mediated ATP hydrolysis (conc. required for 50% stimulation= 10-12, μM), suggesting that this alkaloid seems to interact with drug-binding site of Pgp. Consistent with this view, stemofoline inhibited the photo-crosslinking of Pgp with [125I]-iodoarylazidoprazosin (IAAP), which is a transport substrate. Interestingly, stemofoline instead of inhibiting verapamil-stimulated ATP hydrolysis, it further enhanced the ATPase activity suggesting that stemofoline and verapamil bind simultaneously to Pgp in the drug-binding pocket. In addition, the efflux of the fluorescent substrate calcein-AM from P-gp expressing cervical cancer cells (KB-V1) was blocked by stemofoline in a concentration-dependent manner.Conclusion: These studies indicate that stemofoline could be developed as a potent modulator to overcome MDR in cancer cells.Citation Format: Shinobu Ohnuma, Wisinee Chanmahasathien, Koh Miura, Michiaki Unno, Suresh V. Abudkar, Pornngarm Limtrakul. Stemofoline is a potent natural product modulator of the multidrug resistance-linked P-glycoprotein (ABCB1). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 952. doi:10.1158/1538-7445.AM2013-952" @default.
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- W2148736073 date "2013-04-15" @default.
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- W2148736073 title "Abstract 952: Stemofoline is a potent natural product modulator of the multidrug resistance-linked P-glycoprotein (ABCB1)." @default.
- W2148736073 doi "https://doi.org/10.1158/1538-7445.am2013-952" @default.
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