Modulation of cyclins, p53 and mitogen-activated protein kinases signaling in breast cancer cell lines by 4-(3,4,5-trimethoxyphenoxy)benzoic acid.

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.

• Authors: Kuan-Han Lee, Wen-Yueh Ho, Shu-Jing Wu, Hany A Omar, Po-Jui Huang, Clay C C Wang, Jui-Hsiang Hung
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 15 Issue 1 Pg. 743-57 (Jan 08 2014) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 24406729 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 4-(3,4,5-trimethoxyphenoxy)benzoic acid
• Antineoplastic Agents
• Benzoates
• Cyclins
• Phenyl Ethers
• Tumor Suppressor Protein p53
• Mitogen-Activated Protein Kinases

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Apoptosis (drug effects)
• Benzoates (chemical synthesis, chemistry, pharmacology)
• Breast Neoplasms (metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cyclins (metabolism)
• Female
• G2 Phase Cell Cycle Checkpoints (drug effects)
• HeLa Cells
• Hep G2 Cells
• Humans
• M Phase Cell Cycle Checkpoints (drug effects)
• MCF-7 Cells
• Mitogen-Activated Protein Kinases (metabolism)
• Phenyl Ethers (chemical synthesis, chemistry, pharmacology)
• Phosphorylation (drug effects)
• Signal Transduction (drug effects)
• Tumor Suppressor Protein p53 (metabolism)