Modulation of Cyclins, p53 and Mitogen-Activated Protein Kinases Signaling in Breast Cancer Cell Lines by 4-(3,4,5-Trimethoxyphenoxy)benzoic Acid

doi:10.3390/ijms15010743

CNU IR > Pharmacy and Science > Dept. of Pharmacy > Periodical Articles > Item 310902800/28623

Please use this identifier to cite or link to this item: https://ir.cnu.edu.tw/handle/310902800/28623

Title:	Modulation of Cyclins, p53 and Mitogen-Activated Protein Kinases Signaling in Breast Cancer Cell Lines by 4-(3,4,5-Trimethoxyphenoxy)benzoic Acid
Authors:	Lee, Kuan-Han Ho, Wen-Yueh Wu, Shu-Jing Omar, Hany A. Huang, Po-Jui Wang, Clay C. C. Hung, Jui-Hsiang
Contributors:	藥學系化粧品應用與管理系保健營養系生物科技系新藥創建研究中心
Keywords:	cyclins MCF-7 apoptosis p53 MDA-468 MAPK kinases 4-(3,4,5-trimethoxyphenoxy)benzoic acid
Date:	2014-01
Issue Date:	2015-05-06 21:22:54 (UTC+8)
Publisher:	Mdpi Ag
Abstract:	Despite the advances in cancer therapy and early detection, breast cancer remains a leading cause of cancer-related deaths among females worldwide. The aim of the current study was to investigate the antitumor activity of a novel compound, 4-(3,4,5-trimethoxyphenoxy)benzoic acid (TMPBA) and its mechanism of action, in breast cancer. Results indicated the relatively high sensitivity of human breast cancer cell-7 and MDA-468 cells towards TMPBA with IC50 values of 5.9 and 7.9 mu M, respectively compared to hepatocarcinoma cell line Huh-7, hepatocarcinoma cell line HepG2, and cervical cancer cell line Hela cells. Mechanistically, TMPBA induced apoptotic cell death in MCF-7 cells as indicated by 4 ',6-diamidino-2-phenylindole (DAPI) nuclear staining, cell cycle analysis and the activation of caspase-3. Western blot analysis revealed the ability of TMPBA to target pathways mediated by mitogen-activated protein (MAP) kinases, 5 ' adenosine monophosphate-activated protein kinase (AMPK), and p53, of which the concerted action underlined its antitumor efficacy. In addition, TMPBA induced alteration of cyclin proteins' expression and consequently modulated the cell cycle. Taken together, the current study underscores evidence that TMPBA induces apoptosis in breast cancer cells via the modulation of cyclins and p53 expression as well as the modulation of AMPK and mitogen-activated protein kinases (MAPK) signaling. These findings support TMPBA's clinical promise as a potential candidate for breast cancer therapy.
Relation:	International Journal of Molecular Sciences, v.15 n.1, pp.743-757
Appears in Collections:	[Dept. of Biotechnology (including master's program)] Periodical Articles [Dept. of Health and Nutrition (including master's program)] Periodical Articles [Dept. of Cosmetic Science and institute of cosmetic science] Periodical Articles [Dept. of Pharmacy] Periodical Articles

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