Ethoxysanguinarine Induces Inhibitory Effects and Downregulates CIP2A in Lung Cancer Cells

Zi Liu; Liang Ma; Zhe-Sheng Wen; Yong-Xian Cheng; Guang-Biao Zhou

doi:10.1021/ml400341k

Ethoxysanguinarine Induces Inhibitory Effects and Downregulates CIP2A in Lung Cancer Cells

ACS Med Chem Lett. 2013 Dec 20;5(2):113-8. doi: 10.1021/ml400341k. eCollection 2014 Feb 13.

Authors

Zi Liu¹, Liang Ma², Zhe-Sheng Wen³, Yong-Xian Cheng⁴, Guang-Biao Zhou²

Affiliations

¹ Division of Molecular Carcinogenesis and Targeted Therapy for Cancer, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101, China ; University of Chinese Academy of Sciences , Beijing 100049, China.
² Division of Molecular Carcinogenesis and Targeted Therapy for Cancer, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101, China.
³ Department of Thoracic Surgery, The Cancer Hospital, Sun Yat-Sen University , Guangzhou 510080, China.
⁴ State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences , Kunming 650201, China.

Abstract

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein that is able to stabilize c-Myc oncogenic transcription factor and promote proliferation and transformation of cells. CIP2A is overexpressed in many primary tumors, and pharmacological inactivation of CIP2A is an emerging concept for the development of novel anticancer agents. In this study, we demonstrate that overexpression of CIP2A predicts poor prognosis in lung cancer, and a natural compound, ethoxysanguinarine (ESG), effectively downregulates CIP2A protein and its downstream signaling molecules, c-Myc and pAkt, and induces protein phosphatase 2A (PP2A) activity. ESG inhibits proliferation and induces apoptosis of lung cancer cells, and enhances the effects of cisplatin on malignant cells. Taken together, our findings demonstrate that CIP2A is inversely associated with the clinical outcome of lung cancer, and ESG can serve as a lead compound for the development of CIP2A inhibitor for cancer therapies.

Keywords: CIP2A; Ethoxysanguinarine; apoptosis; cell proliferation; lung cancer.