C21 Steroid-enriched Fraction Refined from Inhibits Hepatocellular Carcinoma Through the Coordination of Hippo-Yap and PTEN-PI3K/AKT Signaling Pathways

Overview

Journal Oncotarget

Specialty Oncology

Date 2018 Jan 5

PMID 29299170

Citations 10

Authors

Yu Zhang

Kaiqiang Li

Youmin Ying

Bingyu Chen

Ke Hao

Boxu Chen

Yu Zheng

Jianxin Lyu

Xiangming Tong

Xiaopan Chen

Ying Wang

Zhajun Zhan

Wei Zhang

Zhen Wang

Affiliations

Soon will be listed here.

Abstract

extraction (MTE), a traditional herbal medicine, has exhibited anti-tumor effects on a variety of cancers. However, its effectiveness and the mechanism of action in Hepatocellular carcinoma (HCC) has not been fully understood. In the present study, we demonstrate that C21 steroid-enriched fraction from MTE, which contains five main C21 steroids (FR5) exhibits obvious pharmacological activities on HCC cells . FR5 induces apoptosis and inhibits proliferation and migration of HepG2 and Bel7402 cells in a dose and time dependent manner. Furthermore, in HCC cells, we found that FR5 inhibits Hippo pathway, leading to inactivation of YAP and increase of PTEN. Enhanced PTEN results in the inhibition of PI3K/AKT signaling pathway, inhibiting cell proliferation by FR5 and FR5-induced apoptosis. Moreover, it was proved that FR5 treatment could inhibit tumor growth in a HCC xenograft mouse model, and immunohistochemistry results showed FR5 treatment resulted in down-regulation of Bcl-2 and YAP, and up-regulation of PTEN and PI3K. Taken together, we found that FR5 effectively inhibits proliferation and induces apoptosis of HCC cells through coordinated inhibition of YAP in the Hippo pathway and AKT in the PI3K-PTEN-mTOR pathway, and suggest FR5 as a potential therapy for HCC.

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