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

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.

• Authors: Min-Hua Wu, Chia-Liang Lin, Hui-Ling Chiou, Shun-Fa Yang, Ching-Yi Lin, Chung-Jung Liu, Yi-Hsien Hsieh
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 19 Issue 1 (Dec 21 2017) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 29267213 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Coumarins
• Drugs, Chinese Herbal
• Flavonoids
• Matrix Metalloproteinase Inhibitors
• Protein Kinase Inhibitors
• TIMP2 protein, human
• praeruptorin A
• Tissue Inhibitor of Metalloproteinase-2
• Matrix Metalloproteinase 2
• Tetradecanoylphorbol Acetate
• 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

Topics

• Antineoplastic Agents (pharmacology)
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Coumarins (pharmacology)
• Drugs, Chinese Herbal (pharmacology)
• Female
• Flavonoids (pharmacology)
• HeLa Cells
• Humans
• MAP Kinase Signaling System (drug effects)
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase Inhibitors (pharmacology)
• Protein Kinase Inhibitors (pharmacology)
• Signal Transduction (drug effects)
• Tetradecanoylphorbol Acetate (pharmacology)
• Tissue Inhibitor of Metalloproteinase-2 (metabolism)
• Uterine Cervical Neoplasms (metabolism)