Genipin induced apoptosis associated with activation of the c-Jun NH2-terminal kinase and p53 protein in HeLa cells.
Genipin is a metabolite of geniposide isolated from an extract of Gardenia fructus. Some observations suggested that genipin could induce cell apoptosis in hepatoma cells and PC3 human prostate cancer cells. However, the effects of genipin on HeLa human cervical carcinoma cells are still unknown. In this study, we provided evidences that genipin induced the death of HeLa cells through apoptotic pathway in a dose-dependent manner. Genipin could remarkably induce cytotoxicity in HeLa cells and inhibit its proliferation. Induction of the apoptosis by genipin was confirmed by analysis of DNA fragmentation and induction of sub-G(1) peak through flow cytometry. The results also showed that genipin-treated HeLa cells cycle was arrested at G(1) phase. Western blot analysis revealed that the phosphorylated c-Jun NH(2)-terminal kinase (JNK) protein, phospho-Jun protein, p53 protein and bax protein significantly increased in a dose-dependent manner after treatment of genipin for 24 h, and to our knowledge, the activation of JNK maybe result in the increase of the p53 protein level, and the increase of the p53 protein led to the accumulation of bax protein, bax protein further induced cell apoptotic death eventually. Taken all these together, it is possible to develop genipin as an anti-cancer drug.
Cao
Houli
H
Key Laboratory of Bio-resources and Eco-environment (Ministry of Education), College of Life Science, Sichuan University, Sichuan, China.
Feng
Qian
Q
Xu
Wei
W
Li
Xiaorong
X
Kang
Zhuang
Z
Ren
Yanqin
Y
Du
Linfang
L
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D057889:Iridoid Glycosides / Q000494:pharmacology*; D039823:Iridoids; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008516:Medicine, Chinese Traditional; D008858:Microscopy, Phase-Contrast; D010766:Phosphorylation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; D057889:Iridoid Glycosides; D039823:Iridoids; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C007834:genipin; D048031:JNK Mitogen-Activated Protein Kinases