title: Induction of apoptosis and histone hyperacetylation by diallyl disulfide in prostate cancer cell line PC-3.
abstract: Prostate cancer is the most invasive and frequently occurred cancer in men. In the initial stages, it is androgen dependent and the androgen ablation therapy is effective at this stage. In the final stages, it becomes androgen-independent and is unresponsive to androgen ablation therapy. At this stage, induction of apoptosis is considered as a better strategy to control cancer. Histone acetylation and deacetylation are involved in transcriptional activation and transcriptional repression, respectively. Diallyl disulfide (DADS) induced histone hyperacetylation can be correlated with the expression of antiproliferative genes. Induction of apoptosis by DADS has been correlated with histone acetylation. In the present study, DADS, oil soluble organosulfur compound of garlic, has been studied for its effect on histone acetylation and induction of apoptosis in prostate cancer cells in vitro. The induction of apoptosis has been demonstrated by annexin V-FITC binding assay. Extent of apoptosis has been assessed measuring the activity of caspase-3. The results have shown that DADS induced apoptosis in prostate cancer cells in a dose dependent manner. At both 25 and 40 microM concentrations, DADS increased the number of both early and late apoptotic cells. Histone hyperacetylation was also observed in DADS treated cells. It is concluded that DADS, induces apoptosis by influencing histone acetylation in prostate cancer cells.
authors.affiliation: Department of Endocrinology, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, Tamil Nadu 600 113, India.
authors.forename: Arumugam
authors.initials: A
authors.lastname: Arunkumar
authors.forename: Marati Radhakrishnan
authors.initials: MR
authors.lastname: Vijayababu
authors.forename: Nandagopal
authors.initials: N
authors.lastname: Gunadharini
authors.forename: Gunasekaran
authors.initials: G
authors.lastname: Krishnamoorthy
authors.forename: Jagadeesan
authors.initials: J
authors.lastname: Arunakaran
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000498:Allyl Compounds / Q000494:pharmacology*; D017304:Annexin A5 / Q000737:chemistry / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004220:Disulfides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding / Q000187:drug effects
chemical_list: D000498:Allyl Compounds; D017304:Annexin A5; D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004220:Disulfides; D006657:Histones; C028009:diallyl disulfide; D053148:Caspase 3; D016650:Fluorescein-5-isothiocyanate