Clerosterol from vinegar-baked radix bupleuri modifies drug transport
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Ya Zhao1,2,*, Li-Min Feng1,*, Li-Juan Liu1, Xian Zhang1, Rui-Zhi Zhao1
1Department of Chinese Medicine Property Team, Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
2The Postdoctoral Research Station, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
*These authors have contributed equally to this work
Rui-Zhi Zhao, email: [email protected]
Keywords: clerosterol, transporter, Pgp, Mrp, Oct
Received: August 04, 2016 Accepted: January 24, 2017 Published: February 09, 2017
Vinegar-baked Radix Bupleuri (VBRB) is reportedly used to treat liver cancer when combined with traditional chemotherapy and data show that this combination may modify drug transport. We isolated clerosterol from VBRB and studied its effect on drug transporters in normal or transporter-overexpressing cells. Transporter activity was assayed using cellular substrate concentration and transporter expression with Western blot and RT-qPCR. Clerosterol decreased cisplatin uptake in BRL cells mainly through increasing Mrp2 gene expression. Clerosterol also decreased the uptake of colchicine in HEK 293 cells by increasing both Pgp and Mrp1 activity; in detail, it could increase Pgp protein but had marginal effects on Mrp1 protein and gene expression. Further study showed clerosterol increased OCT2 activity in HEK293-Pgp cells by increasing OCT2 protein and mRNA. Clerosterol could suppress Pgp overexpression but not by regulating protein and gene expression. And clerosterol had marginal effects on Mrp2 and Mrp1 activity in Mrp2- and Mrp1-overexpressing HEK293 cells. Thus, Clerosterol may be an active constituent of VBRB and may work against cancer multidrug resistance by inhibiting Pgp activity.
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