title: Inhibitory effects of β,β-dimethylacrylshikonin on hepatocellular carcinoma in vitro and in vivo.
abstract: β,β-Dimethylacrylshikonin is one of the most abundant naphthoquinones in the root extracts of Lithospermum erythrorhizon Sieb. et Zucc. (Boraginaceae), which have been reported to have antitumor effects. This study evaluated the antiproliferative activity of β,β-dimethylacrylshikonin on human hepatocellular carcinoma (HCC) cells both in vitro and in vivo. In vitro, the MTT assay showed that β,β-dimethylacrylshikonin inhibited the proliferation of SMMC-7721 cells in both dose- and time-dependent manners with its 50% inhibitory concentration (IC(50) ) at 48 h being 15.01 ± 0.76 µg/mL. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) and Hoechst staining detected the characteristics of cell apoptosis in β,β-dimethylacrylshikonin-treated cells and the apoptotic rates of treated groups were increased in a dose-dependent manner. Flow cytometric analysis revealed that β,β-dimethylacrylshikonin could block the cell cycle arrest at G2 phase. Furthermore, β,β-dimethylacrylshikonin down-regulated the mRNA and protein expression of Bcl-2 but up-regulated that of Bax. The cleaved caspase-3 protein was also detected in treated cells. The experiment in vivo showed that β,β-dimethylacrylshikonin significantly suppressed the growth of H(22) transplantable hepatoma, and induced the activation of caspase-3 determined by immunohistochemistry. The results indicate that β,β-dimethylacrylshikonin has significant antitumor effects on hepatocellular carcinoma both in vitro and in vivo.
authors: Department of Pharmacology, West China Center of Medical Sciences, Sichuan University, Chengdu, Sichuan, China.
authors: Yi-ying
authors: YY
authors: Wu
authors: Li-hong
authors: LH
authors: Wan
authors: Xiao-wei
authors: XW
authors: Zheng
authors: Zhen-jun
authors: ZJ
authors: Shao
authors: Jian
authors: J
authors: Chen
authors: Xia-jing
authors: XJ
authors: Chen
authors: Li-tao
authors: LT
authors: Liu
authors: Wen-juan
authors: WJ
authors: Kuang
authors: Xian-shu
authors: XS
authors: Tan
authors: Li-ming
authors: LM
authors: Zhou
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D029684:Lithospermum / Q000737:chemistry*; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy; D008297:Male; D051379:Mice; D009285:Naphthoquinones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000235:genetics
chemical_list: D000880:Anthraquinones; D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; D009285:Naphthoquinones; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; C073943:beta,beta-dimethylacryshikonin; D053148:Caspase 3