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

Wu, Min-Hua; Lin, Chia-Liang; Chiou, Hui-Ling; Yang, Shun-Fa; Lin, Ching-Yi; Liu, Chung-Jung; Hsieh, Yi-Hsien

doi:10.3390/ijms19010010

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

^1,2,

³,

⁴,

^1,5

⁶,

^7,8,*

and

Yi-Hsien Hsieh

^3,9,10,*

Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan

Department of Laboratory, Chung-Kang Branch, Cheng-Ching General Hospital, Taichung 40764, Taiwan

Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung 40201, Taiwan

⁴

School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung 40201, Taiwan

⁵

Department of Medical Research, Chung Shan Medical University Hospital, Taichung 40201, Taiwan

⁶

Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40201, Taiwan

⁷

Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan

⁸

Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan

⁹

Department of Biochemistry, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan

¹⁰

Clinical laboratory, Chung Shan Medical University Hospital, Taichung 40201, Taiwan

Authors to whom correspondence should be addressed.

Int. J. Mol. Sci. 2018, 19(1), 10; https://doi.org/10.3390/ijms19010010

Received: 19 September 2017 / Revised: 16 December 2017 / Accepted: 19 December 2017 / Published: 21 December 2017

(This article belongs to the Special Issue Natural Bioactives and Phytochemicals in Cancer Prevention)

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Abstract

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. View Full-Text

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

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MDPI and ACS Style

Wu, M.-H.; Lin, C.-L.; Chiou, H.-L.; Yang, S.-F.; Lin, C.-Y.; Liu, C.-J.; Hsieh, Y.-H. Praeruptorin A Inhibits Human Cervical Cancer Cell Growth and Invasion by Suppressing MMP-2 Expression and ERK1/2 Signaling. Int. J. Mol. Sci. 2018, 19, 10. https://doi.org/10.3390/ijms19010010

AMA Style

Wu M-H, Lin C-L, Chiou H-L, Yang S-F, Lin C-Y, Liu C-J, Hsieh Y-H. Praeruptorin A Inhibits Human Cervical Cancer Cell Growth and Invasion by Suppressing MMP-2 Expression and ERK1/2 Signaling. International Journal of Molecular Sciences. 2018; 19(1):10. https://doi.org/10.3390/ijms19010010

Chicago/Turabian Style

Wu, Min-Hua, Chia-Liang Lin, Hui-Ling Chiou, Shun-Fa Yang, Ching-Yi Lin, Chung-Jung Liu, and Yi-Hsien Hsieh. 2018. "Praeruptorin A Inhibits Human Cervical Cancer Cell Growth and Invasion by Suppressing MMP-2 Expression and ERK1/2 Signaling" International Journal of Molecular Sciences 19, no. 1: 10. https://doi.org/10.3390/ijms19010010

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

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