title: Antitumor activity of di-n-butyl-(2,6-difluorobenzohydroxamato)tin(IV) against human gastric carcinoma SGC-7901 cells via G2/M cell cycle arrest and cell apoptosis.
abstract: Di-n-butyl-(2,6-difluorobenzohydroxamato)Tin(IV) (DBDFT), a potential antitumor agent against malignancies, exhibited high activities both in vitro and in vivo. Flow cytometric analysis showed that treatment with DBDFT against Human Gastric Carcinoma (SGC-7901) cells induced a concentration and time-dependent cell accumulation in the G2/M phase of the cell cycle with a parallel depletion of the percentage of cells in G0/G1, the cell apoptosis was observed by characteristic morphological changes and AnnexinV/PI dual-immunofluorescence staining. Fluorescence quantitative FQ- PCR and western blot results showed that G2/M-phase arrest was correlated with up-regulation of cyclin dependent kinase inhibitor p21, Chk2 and CyclinB1, whereas the expressions of other G2/M regulatory check-point protein, Cdc2, and feedback loop protein Cdc25C were obviously down-regulated in a p53-independent manner after the SGC-7901 cells were treated with DBDFT (2.5, 5.0, 7.5 µmol·L(-1)) compared with the control. Furthermore, the up-regulation of Bax and down-regulation of Bcl-2 as well as the activation of caspase-3 were observed, which indicated that DBDFT treatment triggered the mitochondrial apoptotic pathway with an increase of Bax/Bcl-2 ratios, resulting in mitochondrial membrane potential loss and caspase-9 activation in DBDFT treated SGC-7901 cells. In summary, the results illustrated the involvement of multiple signaling pathways targeted by DBDFT in mediating G2/M cell cycle arrest and apoptosis in SGC-7901 cells, which suggested that DBDFT might have therapeutic potential against gastric carcinoma as an effective compound.
authors.affiliation: School of Pharmaceutical Science, Shanxi Medical University, Taiyuan, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Yunlan
authors.affiliation: School of Pharmaceutical Science, Shanxi Medical University, Taiyuan, People's Republic of China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Juan
authors.affiliation: School of Pharmaceutical Science, Shanxi Medical University, Taiyuan, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Qingshan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D016203:CDC2 Protein Kinase; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D064447:Checkpoint Kinase 2 / Q000235:genetics / Q000378:metabolism; D056744:Cyclin B1 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D009368:Neoplasm Transplantation; D009947:Organotin Compounds / Q000737:chemistry / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D020687:cdc25 Phosphatases / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C534699:CCNB1 protein, human; C493956:CDKN1A protein, human; D056744:Cyclin B1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D006877:Hydroxamic Acids; D009947:Organotin Compounds; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; C000594004:di-n-butyl-(2,6-difluorobenzohydroxamato)tin(IV); D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases; D053148:Caspase 3