Preprint Article Version 1 This version not peer reviewed

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

Version 1 : Received: 19 September 2017 / Approved: 19 September 2017 / Online: 19 September 2017 (07:45:00 CEST)

A peer-reviewed article of this Preprint also exists.

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. 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.

Journal reference: Int. J. Mol. Sci. 2018, 19, 10
DOI: 10.3390/ijms19010010

Abstract

Praeruptorin A(PA), a naturally existing pyranocumarin, is isolated from the dried root of Peucedanum praeruptorum Dunn. So far the anti-cancer effect and molecular mechanism behind Praeruptorin A action in human cervical cancer HeLa cells remain unknown. In the present study, we find that PA reduces cell proliferation and colony formation of human cervical cancer HeLa cells through inducing cell cycle arrest at G0/G1 phase. PA-upregulated p21 and p27 proteins are observed, accompanied with inhibition of cyclin D1 and S-phase kinase-associated protein 2(Skp2) proteins expression. PA could significantly inhibit migration and invasion of human HeLa cells. Meanwhile, PA significantly reduces invasive protein expression of matrix metalloproteinase-2 (MMP-2), and increases protein expression of tissue inhibitor of metalloproteinase-2 (TIMP-2). PA is observed to possess the capacity in suppressing ERK1/2 activation. PD98059 (ERK specific inhibitor) significantly enhances PA-induced downregulation of MMP-2 expression, and upregulation of TIMP-2 expression. Moreover, we found that PA treatment notably inhibits 12-O-tetradecanoylphorbol-13-acetate(TPA)-upregulated ERK1/2 activation, MMP-2 expression, cellular migration and invasion in human HeLa cells. Taken together, these findings are the first to demonstrate the anti-cancer activity of PA, which may act as a promising therapeutic agent for the treatment of human cervical cancer.

Subject Areas

praeruptorin A; human cervical cancer; ERK; Invasion; MMP-2; TIMP-2

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