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

International Journal of Molecular Sciences

Kuan-Han Lee³  Wen-Yueh Ho⁵  Shu-Jing Wu⁶  Hany A. Omar⁴  Po-Jui Huang¹  Clay C. C. Wang² 

[1] Department of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan; E-Mail:;Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, Los Angeles, CA 90089, USA; E-Mail:;Department of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan 71710, Taiwan; E-Mail:;Department of Pharmacology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt; E-Mail:;Department of Cosmetic Science and Institute of Cosmetic Science, Chia Nan University of Pharmacy and Science, Tainan 71710, Taiwan; E-Mail:;Department of Nutritional Health, Chia Nan University of Pharmacy and Science, Tainan 71710, Taiwan; E-Mail:

关键词: 4-(3;    4;    5-trimethoxyphenoxy)benzoic acid;    MCF-7;    MDA-468;    apoptosis;    MAPK kinases;    p53;    cyclins;   

DOI  :  10.3390/ijms15010743

来源: mdpi

【 摘 要 】

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 μM, 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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland