(-)-Oleocanthal Inhibits Growth and Metastasis by Blocking Activation of STAT3 in Human Hepatocellular Carcinoma

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 Jun 4

PMID 27259268

Citations 36

Authors

Tiemin Pei

Qinghui Meng

Jihua Han

Haobo Sun

Long Li

Ruipeng Song

Boshi Sun

Shangha Pan

Desen Liang

Lianxin Liu

Affiliations

Soon will be listed here.

Abstract

We explored the anti-cancer capacity of (-)-oleocanthal in human hepatocellular carcinoma (HCC). (-)-Oleocanthal inhibited proliferation and cell cycle progression and induced apoptosis in HCC cells in vitro and suppressed tumor growth in an orthotopic HCC model. (-)-Oleocanthal also inhibited HCC cell migration and invasion in vitro and impeded HCC metastasis in an in vivo lung metastasis model. ( )-Oleocanthal acted by inhibiting epithelial-mesenchymal transition (EMT) through downregulation Twist, which is a direct target of STAT3. (-)-Oleocanthal also reduced STAT3 nuclear translocation and DNA binding activity, ultimately downregulating its downstream effectors, including the cell cycle protein Cyclin D1, the anti-apoptotic proteins Bcl-2 and survivin, and the invasion-related protein MMP 2. Overexpression of constitutively active STAT3 partly reversed the anti cancer effects of (-)-oleocanthal, which inhibited STAT3 activation by decreasing the activities of JAK1 and JAK2 and increasing the activity of SHP-1. These data suggest that (-)-oleocanthal may be a promising candidate for HCC treatment.

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