Apoptotic activity of a new jasmonate analogue is associated with its induction of DNA damage.
The current study was undertaken to investigate the effects of methyl 5-chloro-4,5-didehydrojasmonate (J7), an analogue of methyl jasmonate, on the in vitro growth of human cervical carcinoma HeLa cells. Significantly decreased rates of viability (IC50 approximately 15 microM) as well as evidence of apoptosis were observed with J7. Cell morphological changes observed under light microscopy confirmed apoptosis occurrence. Furthermore, the results from Annexin V-FITC/PI double staining and the cell cycle arrest assay indicated that J7 induced earlier apoptosis of HeLa cells. J7 also reduced the expression of Bcl-2 and subsequent activation of a protease cascade involving caspase-9 and -3 by Western blot assay was observed. We also found that J7 was able to induce DNA damage. These findings suggest that J7 induces HeLa cell apoptosis by activation of caspase pathway and the apoptotic effect is associated with DNA damage. Therefore, J7 may be a candidate compound to be developed into an anticancer agent.
Zhao
Jing
J
Department of Biomedicinal Chemistry and Institute of Basic Sciences, Inje University, Gimhae 621-749, Korea.
Kang
Saeromi
S
Zhang
Xin
X
You
Song
S
Park
Jang-Su
JS
Jung
Jee H
JH
Kim
Dong-Kyoo
DK
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003517:Cyclopentanes / Q000494:pharmacology*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
C553470:5-chloro-4,5-didehydrojasmonate; D000970:Antineoplastic Agents; D003517:Cyclopentanes; D005231:Fatty Acids, Unsaturated; D019253:Proto-Oncogene Proteins c-bcl-2; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9