Rottlerin Exhibits Anti-cancer Effect Through Inactivation of S Phase Kinase-associated Protein 2 in Pancreatic Cancer Cells

Overview

Journal Am J Cancer Res

Specialty Oncology

Date 2016 Nov 9

PMID 27822410

Citations 24

Authors

Jingna Su

Lixia Wang

Xuyuan Yin

Zhe Zhao

Yingying Hou

Xiantao Ye

Xiuxia Zhou

Zhiwei Wang

Affiliations

Soon will be listed here.

Abstract

Rottlerin, a natural product isolated from Mallotus philippinensis, has been characterized as an effective chemoprevention agent in inhibiting tumor cell growth. Although multiple studies have revealed the role of rottlerin in tumorigenesis, the molecular mechanism of rottlerin-mediated anti-tumor activity has not been fully elucidated. It has been reported that Skp2 (S-phase kinase associated protein 2) plays an oncogenic role in human malignancies, indicating that inactivation of Skp2 could be a promising approach for the treatment of cancers. Therefore, in this study, we aim to investigate whether rottlerin exhibits its anti-tumor activities via targeting Skp2 pathway in pancreatic cancer. We found that rottlerin inhibited cell growth, induced apoptosis, arrested cell cycle, and retarded cell invasion and migration. Notably, we observed that the expression of Skp2 was significantly decreased in rottlerin-treated pancreatic cancer cells. Importantly, overexpression of Skp2 abrogated the anti-tumor function induced by rottlerin in pancreatic cancer cells. Consistently, depletion of Skp2 promoted rottlerin-mediated inhibition of cell growth and invasion. Collectively, our study demonstrated that rottlerin could suppress Skp2 expression and subsequently exert its tumor suppressive function in pancreatic cancer cells, suggesting that rottlerin might be a potential therapeutic compound for treating pancreatic cancer.

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