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Teratogenic Jervine Increases the Activity of Doxorubicin in MCF-7/ADR Cells by Inhibiting ABCB1

Teratogenic Jervine Increases the Activity of Doxorubicin in MCF-7/ADR Cells by Inhibiting ABCB1

Ming Liu, Xuxiu Lu, Jinman Zhang, Xingzeng Zhao, Wei Zhang, Xiukun Lin

Biomed Pharmacother. 2019 Sep;117:109059.

PMID: 31207578

Abstract:

Jervine is a natural teratogenic compound isolated from Veratrum californicum. In this study, for the first time, we revealed a novel activity of jervine in sensitizing the anti-proliferation effect of doxorubicin (DOX). We demonstrated that the synergistic mechanism was related to the intracellular accumulation of DOX via modulating ABCB1 transportation. Jervine did not affect the expression of ABCB1 in mRNA nor protein levels. However, jervine increased the ATPase activity of ABCB1 and possibly served as a substrate of ABCB1. The molecular docking results indicated that jervine was bound to a closed ABCB1 conformation and blocked drug entrance to the central binding site at the transmembrane domain. The present study identifies jervine acts as a substrate of ABCB1, and has potential to be developed as a novel and potent chemotherapy sensitizer used for patients developing multidrug resistance.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP469590-A	Jervine		469-59-0	Price

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