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Int. J. Mol. Sci. 2015, 16(4), 7577-7586; doi:10.3390/ijms16047577

Poly-γ-Glutamic Acid Induces Apoptosis via Reduction of COX-2 Expression in TPA-Induced HT-29 Human Colorectal Cancer Cells

1
Department of Food Biotechnology, University of Science & Technology, 217 Gajeong-ro, Yuseong-gu, Daejeon 305-333, Korea
2
Korea Food Research Institute, 1201 Anyangpangyoro, Bundang-gu, Seongnam-si, Gyeonggi-do 463-746, Korea
*
Author to whom correspondence should be addressed.
Academic Editor: Sanjay K. Srivastava
Received: 28 November 2014 / Revised: 24 March 2015 / Accepted: 30 March 2015 / Published: 3 April 2015
(This article belongs to the Special Issue Bioactive Phytochemicals in Functional Foods for Cancer Prevention)
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Abstract

Poly-γ-glutamic acid (PGA) is one of the bioactive compounds found in cheonggukjang, a fast-fermented soybean paste widely utilized in Korean cooking. PGA is reported to have a number of beneficial health effects, and interestingly, it has been identified as a possible anti-cancer compound through its ability to promote apoptosis in cancer cells, although the precise molecular mechanisms remain unclear. Our findings demonstrate that PGA inhibits the pro-proliferative functions of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), a known chemical carcinogen in HT-29 human colorectal cancer cells. This inhibition was accompanied by hallmark apoptotic phenotypes, including DNA fragmentation and the cleavage of poly (ADP-ribose) polymerase (PARP) and caspase 3. In addition, PGA treatment reduced the expression of genes known to be overexpressed in colorectal cancer cells, including cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS). Lastly, PGA promoted activation of 5' adenosine monophosphate-activated protein (AMPK) in HT-29 cells. Taken together, our results suggest that PGA treatment enhances apoptosis in colorectal cancer cells, in part by modulating the activity of the COX-2 and AMPK signaling pathways. These anti-cancer functions of PGA make it a promising compound for future study. View Full-Text
Keywords: poly-γ-glutamic acid; HT-29 human colorectal cancer cell; apoptosis; cyclooxygenase; AMP-activated protein kinase poly-γ-glutamic acid; HT-29 human colorectal cancer cell; apoptosis; cyclooxygenase; AMP-activated protein kinase
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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. (CC BY 4.0).

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MDPI and ACS Style

Shin, E.J.; Sung, M.J.; Park, J.H.; Yang, H.J.; Kim, M.S.; Hur, H.J.; Hwang, J.-T. Poly-γ-Glutamic Acid Induces Apoptosis via Reduction of COX-2 Expression in TPA-Induced HT-29 Human Colorectal Cancer Cells. Int. J. Mol. Sci. 2015, 16, 7577-7586.

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