title: Reactive oxygen species-mitochondria pathway involved in FV-429-induced apoptosis in human hepatocellular carcinoma HepG2 cells.
abstract: FV-429 is a newly synthesized flavonoid with a bis(2-hydroxyethyl) amino propoxy substitution. In this study, we investigate the anticancer effect of FV-429 both in vivo and in vitro. These data have shown that FV-429 could significantly inhibit tumor growth in mice inoculated with Heps hepatoma cells without evident toxicity. After the treatment of FV-429 (40 mg/kg), the inhibitory rate of tumor weight was 52.12%. Then, we performed diamidinophenylindole staining and annexin V/propidium iodide double-staining assay to investigate the apoptosis induced by FV-429 in HepG2 cells. Further research revealed that FV-429 induced apoptosis through the mitochondrial apoptotic pathway, as indicated by a change in Bax/Bcl-2 ratios, collapse of mitochondrial membrane potential, the transposition of apoptotic-inducing factor and cytochrome c, caspase-3 and caspase-9 activation, and degradation of poly (ADP-ribose) polymerase. The accumulation of reactive oxygen species induced by FV-429 in HepG2 cells was also observed. Moreover, the mitogen-activated protein kinases, the downstream effect of reactive oxygen species accumulation including c-Jun N-terminal kinase and p38 mitogen-activated protein kinases, could be activated by FV-429. Taken together, our results provided a mechanistic framework for further exploration of FV-429 as a novel chemotherapy for human tumors.
authors: Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, People's Republic of China.
authors: Zhen
authors: Z
authors: Yang
authors: Lei
authors: L
authors: Qiang
authors: Tian
authors: T
authors: Wu
authors: Fei-Hong
authors: FH
authors: Chen
authors: Hui-Ying
authors: HY
authors: Yang
authors: Qing
authors: Q
authors: Zhao
authors: Mei-Juan
authors: MJ
authors: Zou
authors: Ya-Jing
authors: YJ
authors: Sun
authors: Zhi-Yu
authors: ZY
authors: Li
authors: Qing-Long
authors: QL
authors: Guo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D056945:Hep G2 Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C569690:FV-429 compound; D005419:Flavonoids; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases