title: Role of di-allyl disulfide, a garlic component in NF-κB mediated transient G2-M phase arrest and apoptosis in human leukemic cell-lines.
abstract: Diallyl disulfide (DADS), the major organosulfur component of processed garlic is very effective in chemoprevention of several types of cancers; however, its detailed mechanism is yet to be divulged. Present study shows antiproliferative activity of DADS against human leukemic cell-lines, mainly U937. DADS induced transient G2/M phase arrest, which is evident from FACS analysis. The results revealed that a significant transcriptional induction of p21 happened in early hours of treatment, which is due to increased nuclear translocation of NF-κB and its specific binding to p21 promoter. However, in the later hours, G2/M arrest is lost leading to apoptosis via intrinsic mitochondria-mediated pathway through generation of reactive oxygen species followed by changes in mitochondrial membrane potential. Western blots indicate release of cytochrome-c, activation of caspase-3, cleavage of PARP1, and finally decrease in bcl-2 levels. In addition, inactivation of NF-κB by its inhibitor BAY 11-7085 causes early onset of apoptosis without any transient G2/M arrest. Thus, in conclusion, DADS induces reversible G2/M arrest through NF-κB mediated pathway in human leukemic cell lines, like U937, K562, and Jurkat, lacking wild type p53. However, G2/M arrest is lost owing to the incapability of the damage repair system that leads to apoptosis.
authors: Department of Biophysics, Molecular Biology and Bioinformatics, University of Calcutta, Kolkata, India.
authors: Pritha
authors: P
authors: Dasgupta
authors: Sumita Sengupta
authors: SS
authors: Bandyopadhyay
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D004220:Disulfides / Q000494:pharmacology*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D005737:Garlic / Q000737:chemistry; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009570:Nitriles; D013450:Sulfones
chemical_list: D000498:Allyl Compounds; D000972:Antineoplastic Agents, Phytogenic; C416282:BAY 11-7085; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004220:Disulfides; D016328:NF-kappa B; D009570:Nitriles; D013450:Sulfones; C028009:diallyl disulfide