title: Poly-γ-glutamic acid induces apoptosis via reduction of COX-2 expression in TPA-induced HT-29 human colorectal cancer cells.
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.
authors: Department of Food Biotechnology, University of Science & Technology, 217 Gajeong-ro, Yuseong-gu, Daejeon 305-333, Korea. sej296@hanmail.net.|Korea Food Research Institute, 1201 Anyangpangyoro, Bundang-gu, Seongnam-si, Gyeonggi-do 463-746, Korea. sej296@hanmail.net.
authors: Eun Ju
authors: EJ
authors: Shin
authors: Department of Food Biotechnology, University of Science & Technology, 217 Gajeong-ro, Yuseong-gu, Daejeon 305-333, Korea. dulle5@kfri.re.kr.|Korea Food Research Institute, 1201 Anyangpangyoro, Bundang-gu, Seongnam-si, Gyeonggi-do 463-746, Korea. dulle5@kfri.re.kr.
authors: Mi Jeong
authors: MJ
authors: Sung
authors: Department of Food Biotechnology, University of Science & Technology, 217 Gajeong-ro, Yuseong-gu, Daejeon 305-333, Korea. jhpark@kfri.re.kr.|Korea Food Research Institute, 1201 Anyangpangyoro, Bundang-gu, Seongnam-si, Gyeonggi-do 463-746, Korea. jhpark@kfri.re.kr.
authors: Jae Ho
authors: JH
authors: Park
authors: Korea Food Research Institute, 1201 Anyangpangyoro, Bundang-gu, Seongnam-si, Gyeonggi-do 463-746, Korea. yhj@kfri.re.kr.
authors: Hye Jeong
authors: HJ
authors: Yang
authors: Korea Food Research Institute, 1201 Anyangpangyoro, Bundang-gu, Seongnam-si, Gyeonggi-do 463-746, Korea. truka@kfri.re.kr.
authors: Myung Sunny
authors: MS
authors: Kim
authors: Korea Food Research Institute, 1201 Anyangpangyoro, Bundang-gu, Seongnam-si, Gyeonggi-do 463-746, Korea. mismalto@kfri.re.kr.
authors: Haeng Jeon
authors: HJ
authors: Hur
authors: Department of Food Biotechnology, University of Science & Technology, 217 Gajeong-ro, Yuseong-gu, Daejeon 305-333, Korea. jthwang@kfri.re.kr.|Korea Food Research Institute, 1201 Anyangpangyoro, Bundang-gu, Seongnam-si, Gyeonggi-do 463-746, Korea. jthwang@kfri.re.kr.
authors: Jin-Taek
authors: JT
authors: Hwang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011099:Polyglutamic Acid / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D011099:Polyglutamic Acid; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D013755:Tetradecanoylphorbol Acetate