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.

[1]  S. Bao,et al.  Genistein induces G2/M cell cycle arrest and apoptosis of human ovarian cancer cells via activation of DNA damage checkpoint pathways , 2009, Cell biology international.

[2]  Paloma Martin,et al.  Differences in Repair of DNA Cross-links between Lymphocytes and Epithelial Tumor Cells from Colon Cancer Patients Measured In vitro with the Comet Assay , 2009, Clinical Cancer Research.

[3]  Jongki Hong,et al.  New jasmonate analogues as potential anti-inflammatory agents. , 2008, Bioorganic & medicinal chemistry.

[4]  T. Hsia,et al.  DNA damage and endoplasmic reticulum stress mediated curcumin-induced cell cycle arrest and apoptosis in human lung carcinoma A-549 cells through the activation caspases cascade- and mitochondrial-dependent pathway. , 2008, Cancer letters.

[5]  E. Flescher,et al.  Methyl jasmonate induces cell death with mixed characteristics of apoptosis and necrosis in cervical cancer cells. , 2008, Cancer letters.

[6]  Laxmi Yeruva,et al.  Methyl jasmonate decreases membrane fluidity and induces apoptosis through tumor necrosis factor receptor 1 in breast cancer cells , 2008, Anti-cancer drugs.

[7]  Laxmi Yeruva,et al.  Delayed Cytotoxic Effects of Methyl Jasmonate and cis-Jasmone Induced Apoptosis in Prostate Cancer Cells , 2008, Cancer investigation.

[8]  S. Elmore.  Apoptosis: A Review of Programmed Cell Death , 2007, Toxicologic pathology.

[9]  E. Flescher,et al.  Effects of natural and novel synthetic jasmonates in experimental metastatic melanoma , 2007, British journal of pharmacology.

[10]  Qian Peng,et al.  Involvement of both caspase-dependent and -independent pathways in apoptotic induction by hexaminolevulinate-mediated photodynamic therapy in human lymphoma cells , 2006, Apoptosis.

[11]  E. Flescher.  Jasmonates–a new family of anti-cancer agents , 2005, Anti-cancer drugs.

[12]  K. Tanabe,et al.  Caspase-dependent and -independent cell death pathways after DNA damage (Review). , 2005, Oncology reports.

[13]  S. Fulda,et al.  Targeting apoptosis pathways in cancer therapy. , 2004, Current cancer drug targets.

[14]  Boris Zhivotovsky,et al.  DNA damage-induced apoptosis , 2004, Oncogene.

[15]  S. Cory,et al.  The Bcl2 family: regulators of the cellular life-or-death switch , 2002, Nature Reviews Cancer.

[16]  A. Girstun,et al.  SF2/ASF protein inhibits camptothecin-induced DNA cleavage by human topoisomerase I. , 2002, European journal of biochemistry.

[17]  Wenyi Wei,et al.  Role of p21 in Apoptosis and Senescence of Human Colon Cancer Cells Treated with Camptothecin* , 2002, The Journal of Biological Chemistry.

[18]  E. Flescher,et al.  Plant stress hormones suppress the proliferation and induce apoptosis in human cancer cells , 2002, Leukemia.

[19]  N. Singh,et al.  Microgels for estimation of DNA strand breaks, DNA protein crosslinks and apoptosis. , 2000, Mutation research.

[20]  M. Hengartner.  The biochemistry of apoptosis , 2000, Nature.

[21]  J. Martinou,et al.  Mitochondria as the central control point of apoptosis. , 2000, Trends in cell biology.

[22]  T. Hamamoto,et al.  A water-soluble tetrazolium salt useful for colorimetric cell viability assay , 1999 .

[23]  B. Wouters,et al.  Apoptosis , p 53 , and Tumor Cell Sensitivity to Anticancer Agents 1 , 1999 .

[24]  S. Srinivasula,et al.  Cytochrome c and dATP-Dependent Formation of Apaf-1/Caspase-9 Complex Initiates an Apoptotic Protease Cascade , 1997, Cell.

[25]  A. Young,et al.  Measurement of menadione-mediated DNA damage in human lymphocytes using the comet assay. , 1997, Free radical research.

[26]  G. Hanks,et al.  Radiation inactivation of human prostate cancer cells: the role of apoptosis. , 1996, Radiation research.

[27]  John Calvin Reed,et al.  Immunohistochemical analysis of bcl-2, bax, bcl-X, and mcl-1 expression in prostate cancers. , 1996, The American journal of pathology.

[28]  John Calvin Reed,et al.  Tumor suppressor p53 is a direct transcriptional activator of the human bax gene , 1995, Cell.

[29]  W. Earnshaw,et al.  Nuclear changes in apoptosis. , 1995, Current opinion in cell biology.

[30]  D. Fisher.  Apoptosis in cancer therapy: Crossing the threshold , 1994, Cell.

[31]  John Calvin Reed,et al.  Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. , 1994, Oncogene.