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Int. J. Mol. Sci. 2014, 15(1), 743-757; doi:10.3390/ijms15010743
Article

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

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Received: 19 November 2013; in revised form: 23 December 2013 / Accepted: 30 December 2013 / Published: 8 January 2014
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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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 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.
Keywords: 4-(3,4,5-trimethoxyphenoxy)benzoic acid; MCF-7; MDA-468; apoptosis; MAPK kinases; p53; cyclins 4-(3,4,5-trimethoxyphenoxy)benzoic acid; MCF-7; MDA-468; apoptosis; MAPK kinases; p53; cyclins
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Lee, K.-H.; Ho, W.-Y.; Wu, S.-J.; Omar, H.A.; Huang, P.-J.; Wang, C.C.C.; Hung, J.-H. Modulation of Cyclins, p53 and Mitogen-Activated Protein Kinases Signaling in Breast Cancer Cell Lines by 4-(3,4,5-Trimethoxyphenoxy)benzoic Acid. Int. J. Mol. Sci. 2014, 15, 743-757.

AMA Style

Lee K-H, Ho W-Y, Wu S-J, Omar HA, Huang P-J, Wang CCC, Hung J-H. 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. 2014; 15(1):743-757.

Chicago/Turabian Style

Lee, Kuan-Han; Ho, Wen-Yueh; Wu, Shu-Jing; Omar, Hany A.; Huang, Po-Jui; Wang, Clay C.C.; Hung, Jui-Hsiang. 2014. "Modulation of Cyclins, p53 and Mitogen-Activated Protein Kinases Signaling in Breast Cancer Cell Lines by 4-(3,4,5-Trimethoxyphenoxy)benzoic Acid." Int. J. Mol. Sci. 15, no. 1: 743-757.



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