Induction of apoptosis by genipin inhibits cell proliferation in AGS human gastric cancer cells via Egr1/p21 signaling pathway.
Natural compounds are becoming important candidates in cancer therapy due to their cytotoxic effects on cancer cells by inducing various types of programmed cell deaths. In this study, we investigated whether genipin induces programmed cell deaths and mediates in Egr1/p21 signaling pathways in gastric cancer cells. Effects of genipin in AGS cancer cell lines were observed via evaluation of cell viability, ROS generation, cell cycle arrest, and protein and RNA levels of p21, Egr1, as well as apoptotic marker genes. The cell viability of AGS cells reduced by genipin treatment via induction of the caspase 3-dependent apoptosis. Cell cycle arrest was observed at the G2/M phase along with induction of p21 and p21-dependent cyclins. As an upstream mediator of p21, the transcription factor early growth response-1 (Egr1) upregulated p21 through nuclear translocation and binding to the p21 promoter site. Silencing Egr1 expression inhibited the expression of p21 and downstream molecules involved in apoptosis. We demonstrated that genipin treatment in AGS human gastric cancer cell line induces apoptosis via p53-independent Egr1/p21 signaling pathway in a dose-dependent manner.
Laboratory of Molecular Oncology, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine, Seoul, Republic of Korea.
Hyeonseok
H
Ko
College of Life Sciences & Biotechnology, Korea University, 5-1 Anam-dong, Seongbuk-gu, Seoul 136-701, Republic of Korea.
Jee Min
JM
Kim
College of Life Sciences & Biotechnology, Korea University, 5-1 Anam-dong, Seongbuk-gu, Seoul 136-701, Republic of Korea.
Sun-Joong
SJ
Kim
Department of Microbiology, College of Medicine, Korea University, 5-1 Anam-dong, Seongbuk-gu, Seoul 136-701, Republic of Korea.
So Hee
SH
Shim
Department of Asan Institute for Life Sciences, Asan Medical Center, College of Medicine, University of Ulsan, 86 Asanbyeoungwon-gil, Songpa-gu, Seoul 138-736, Republic of Korea. Electronic address: chhoonha@amc.seoul.kr.
Chang Hoon
CH
Ha
College of Life Sciences & Biotechnology, Korea University, 5-1 Anam-dong, Seongbuk-gu, Seoul 136-701, Republic of Korea. Electronic address: hichang@korea.ac.kr.
Hyo Ihl
HI
Chang
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D039823:Iridoids / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D039823:Iridoids; C094815:NAB1 protein, human; D012097:Repressor Proteins; C007834:genipin
Apoptosis; Egr1; Genipin; Programmed cell death; p21