Cell-cycle specificity of sulforaphane-mediated apoptosis in Jurkat T-leukemia cells.

BACKGROUND Sulforaphane (SFN) is an isothiocyanate that is present in widely consumed vegetables. Previous studies have shown that SFN is effective in preventing carcinogenesis induced by carcinogens in rodents. Recently it was found that SFN could also inhibit cell proliferation and induce apoptosis in several tumor cell lines. In the present study, the possible cell-cycle specificity of SFN-mediated apoptosis was investigated. MATERIALS AND METHODS Cells were synchronized by thymidine block. Analysis of the cell-cycle and apoptosis induction was performed using flow cytometry. RESULTS Flow cytometric assessment of the extent of apoptosis in cells synchronized by thymidine block revealed that cells were most sensitive to SFN in the G -phase, less sensitive in the G2/M-phase and least sensitive during the S-phase. CONCLUSION These findings suggest that cell vulnerability to SFN-mediated apoptosis is subject to regulation by cell-cycle-dependent mechanisms.

[1]  V. Rotter,et al.  Subcellular distribution of the p53 protein during the cell cycle of Balb/c 3T3 cells. , 1990, Oncogene.

[2]  J. Bertino Chemical action and pharmacology of methotrexate, azathioprine and cyclophosphamide in man. , 1973, Arthritis and rheumatism.

[3]  S. Hecht,et al.  Phenethyl isothiocyanate and sulforaphane and their N-acetylcysteine conjugates inhibit malignant progression of lung adenomas induced by tobacco carcinogens in A/J mice. , 2005, Cancer research.

[4]  L. Gamet-Payrastre Signaling pathways and intracellular targets of sulforaphane mediating cell cycle arrest and apoptosis. , 2006, Current cancer drug targets.

[5]  L. Hu,et al.  Cytotoxicity and cell-cycle effects of paclitaxel when used as a single agent and in combination with ionizing radiation. , 1997, International journal of radiation oncology, biology, physics.

[6]  Jinsong Liu,et al.  Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by beta-phenylethyl isothiocyanate. , 2006, Cancer cell.

[7]  Y. Gazitt,et al.  Fluctuations and ultrastructural localization of oncoproteins and cell cycle regulatory proteins during growth and apoptosis of synchronized AGF cells. , 1994, Cancer research.

[8]  A. Levine,et al.  The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation , 1992, Cell.

[9]  P. Shastry,et al.  Upregulation of survivin in G2/M cells and inhibition of caspase 9 activity enhances resistance in staurosporine-induced apoptosis. , 2004, Neoplasia.

[10]  S. Nair,et al.  ERK and JNK signaling pathways are involved in the regulation of activator protein 1 and cell death elicited by three isothiocyanates in human prostate cancer PC-3 cells. , 2006, Carcinogenesis.

[11]  Stephen N. Jones,et al.  Regulation of p53 stability by Mdm2 , 1997, Nature.

[12]  T. Kensler,et al.  Anticarcinogenic activities of sulforaphane and structurally related synthetic norbornyl isothiocyanates. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[13]  P. Hrelia,et al.  Isothiocyanates as novel cytotoxic and cytostatic agents: molecular pathway on human transformed and non-transformed cells. , 2004, Biochemical pharmacology.

[14]  C. Rao,et al.  Chemoprevention of colonic aberrant crypt foci in Fischer rats by sulforaphane and phenethyl isothiocyanate. , 2000, Carcinogenesis.

[15]  M. Oren,et al.  Mdm2 promotes the rapid degradation of p53 , 1997, Nature.

[16]  J. Finley,et al.  Cruciferous Vegetables: Cancer Protective Mechanisms of Glucosinolate Hydrolysis Products and Selenium , 2004, Integrative cancer therapies.

[17]  P. Hrelia,et al.  Growth inhibition, cell-cycle arrest and apoptosis in human T-cell leukemia by the isothiocyanate sulforaphane. , 2002, Carcinogenesis.

[18]  T. Kensler,et al.  Sulforaphane inhibits extracellular, intracellular, and antibiotic-resistant strains of Helicobacter pylori and prevents benzo[a]pyrene-induced stomach tumors , 2002, Proceedings of the National Academy of Sciences of the United States of America.