title: Induction of G₂/M arrest and apoptosis by sulforaphane in human osteosarcoma U2-OS cells.
abstract: Sulforaphane is one of the most abundant isothiocyanates found in certain cruciferous vegetables, particularly broccoli. To date, sulforaphane has gained attention as a chemopreventive compound. The mechanism responsible for the anticancer effects of sulforaphane in osteosarcoma, however, is not clear. In this study, we demonstrate an anti-proliferative mechanism of sulforaphane in human osteosarcoma cells. The treatment of cells with sulforaphane resulted in a concentration- and time‑dependent inhibition of growth and G2/M phase arrest of the cell cycle. This effect was associated with a decrease in protein expression of cyclin A and B1 and their activating partners, cyclin-dependent kinases (CDKs) 1 and 2, with concomitant up-regulation of p21, a CDK inhibitor. Sulforaphane treatment also resulted in apoptosis as evidenced by an increase in annexin V+/propidium iodide- (V+/PI-) cells, the cleavage of 116-kDa poly (ADP-ribose) polymerase (PARP) and ICAD and oligonucleosomal DNA fragmentation. Taken together, these findings indicate that the molecular mechanisms underlying sulforaphane-mediated growth inhibition in U2-OS cells may be the modulation of the cell cycle machinery and the induction of apoptosis.
authors: Department of Orthopaedic Surgery, Medical School, Chonbuk National University, Jeonju, Jeonbuk 561-756, Republic of Korea.
authors: Mi-Ran
authors: MR
authors: Kim
authors: Lu
authors: L
authors: Zhou
authors: Byung-Hyun
authors: BH
authors: Park
authors: Jung Ryul
authors: JR
authors: Kim
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects*; D006801:Humans; D017879:Isothiocyanates; D008938:Mitosis / Q000187:drug effects*; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D017879:Isothiocyanates; D013454:Sulfoxides; D013861:Thiocyanates; C109664:caspase-activated DNase inhibitor; D011065:Poly(ADP-ribose) Polymerases; C016766:sulforaphane