Small Interfering RNA Targeting Rac1 Sensitizes Colon Cancer to Dihydroartemisinin-induced Cell Cycle Arrest and Inhibited Cell Migration by Suppressing NFκB Activity

Overview

Journal Mol Cell Biochem

Publisher Springer

Specialty Biochemistry

Date 2013 Apr 6

PMID 23559092

Citations 8

Authors

Peng Han

Ying Luan

Yanlong Liu

Zhiwei Yu

Jingwen Li

Zicheng Sun

Gang Chen

Binbin Cui

Affiliations

Soon will be listed here.

Abstract

Dihydroartemisinin (DHA) has recently shown antitumor activity in various cancer cells. The small GTPase Rac1 regulates many cellular processes, including cytoskeletal reorganization, cell migration, proliferation, and survival. In addition, Rac1 plays a major role in activating NFκB-mediated transcription. Both Rac1 and NFκB regulate many properties of the malignant phenotype, including anchorage-independent proliferation and survival, metastasis, and angiogenesis. In this study, for the first time, we demonstrated that Rac1 knockdown can enhance DHA-induced growth inhibition, cell cycle arrest, apoptosis, and migration in both HCT116 and RKO cell lines in vitro. The mechanism is due partially to DHA, and Rac1 siRNA deactivates NFκB activity, so as to decrease tremendously the expression of its target gene products, such as PCNA, cyclin D1, and CDK4; and increase the expression of p21, cleaved-caspase-3, and cleaved-PARP. In our in vivo studies, DHA also manifested remarkably enhanced antitumor effect when combined with Rac1 siRNA. We concluded that inhibition of NFκB activation is one of the mechanisms that Rac1 siRNA dramatically promotes DHAs antitumor effect on human colon cancer.

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