title: β,β-Dimethylacrylshikonin induces mitochondria dependent apoptosis through ERK pathway in human gastric cancer SGC-7901 cells.
abstract: β,β-Dimethylacrylshikonin, one of the active components in the root extracts of Lithospermum erythrorhizon, posses antitumor activity. In this study, we discussed the molecular mechanisms of β,β-dimethylacrylshikonin in the apoptosis of SGC-7901 cells. β,β-Dimethylacrylshikonin reduced the cell viability of SGC-7901 cells in a dose- and time-dependent manner and induced cell apoptosis. β,β-Dimethylacrylshikonin treatment in SGC-7901 cells down-regulated the expression of XIAP, cIAP-2, and Bcl-2 and up-regulated the expression of Bak and Bax and caused the loss of mitochondrial membrane potential and release of cytochrome c. Additionally, β,β-dimethylacrylshikonin treatment led to activation of caspases-9, 8 and 3, and cleavage of poly (ADP-ribose) polymerase (PARP), which was abolished by pretreatment with the pan-caspase inhibitor Z-VAD-FMK. β,β-Dimethylacrylshikonin induced phosphorylation of extracellular signal-regulated kinase (ERK) in SGC-7901 cells. U0126, a specific MEK inhibitor, blocked the ERK activation by β,β-dimethylacrylshikonin and abrogated β,β-dimethylacrylshikonin -induced apoptosis. Our results demonstrated that β,β-dimethylacrylshikonin inhibited growth of gastric cancer SGC-7901 cells by inducing ERK signaling pathway, and provided a clue for preclinical and clinical evaluation of β,β-dimethylacrylshikonin for gastric cancer therapy.
authors: Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors: Xiu-Jin
authors: XJ
authors: Shen
authors: Hai-Bing
authors: HB
authors: Wang
authors: Xiao-Qiong
authors: XQ
authors: Ma
authors: Jiang-Hua
authors: JH
authors: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009285:Naphthoquinones / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D013274:Stomach Neoplasms / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents; D009285:Naphthoquinones; C032573:beta, beta-dimethylacrylshikonin; D048049:Extracellular Signal-Regulated MAP Kinases