Praeruptorin A Inhibits Human Cervical Cancer Cell Growth and Invasion by Suppressing MMP-2 Expression and ERK1/2 Signaling

International Journal of Molecular Sciences

Ching-Yi Lin¹  Chung-Jung Liu²  Chia-Liang Lin³  Yi-Hsien Hsieh³  Shun-Fa Yang⁴  Min-Hua Wu⁴  Hui-Ling Chiou⁵ 

[1] Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40201, Taiwan;Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan;Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung 40201, Taiwan;Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan;School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung 40201, Taiwan;

关键词: Praeruptorin A;    cervical cancer cells;    ERK1/2;    invasion;    MMP-2;    TIMP-2;   

DOI  :  10.3390/ijms19010010

来源: DOAJ

【 摘 要 】

Praeruptorin A (PA) is a pyranocumarin present in the dried root of Peucedanumpraeruptorum Dunn that has anticancer effects against several types of cells. However, the effect of PA on human cervical cancer cells is unknown. Our results indicate that PA significantly inhibited cell proliferation, colony formation, migration, invasion, and wound closure of HeLa and SiHa cells, induced cell cycle arrest at G0/G1 phase, upregulated Rb, p16, p21 and p27 proteins and downregulated cyclin D1 and S-phase kinase-associated protein 2 (Skp2) proteins. PA also significantly reduced expression of matrix metalloproteinase-2 (MMP-2) and increased expression of tissue inhibitor of metalloproteinase-2 (TIMP-2). In addition, PA suppressed ERK1/2 activation and increased the effect of PD98059 (a specific MEK1/2 inhibitor) in downregulation of MMP-2 and upregulation of TIMP-2. PA treatment inhibited the effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on upregulation of ERK1/2 activation, MMP-2 expression, cellular migration, and invasion of HeLa cells. Our findings are the first to demonstrate the activity of PA against cervical cancer cells, and suggest this agent has promise as a therapeutic agent in treatment of human cervical cancer.

【 授权许可】

Unknown