title: Effect of β,β-dimethylacrylshikonin on inhibition of human colorectal cancer cell growth in vitro and in vivo.
abstract: In traditional Chinese medicine, shikonin and its derivatives, has been used in East Asia for several years for the prevention and treatment of several diseases, including cancer. We previously identified that β,β-dimethylacrylshikonin (DA) could inhibit hepatocellular carcinoma growth. In the present study, we investigated the inhibitory effects of DA on human colorectal cancer (CRC) cell line HCT-116 in vitro and in vivo. A viability assay showed that DA could inhibit tumor cell growth in a time- and dose-dependent manner. Flow cytometry showed that DA blocks the cell cycle at G(0)/G(1) phase. Western blotting results demonstrated that the induction of apoptosis by DA correlated with the induction of pro-apoptotic proteins Bax, and Bid, and a decrease in the expression of anti-apoptotic proteins Bcl-2 and Bcl-xl. Furthermore, treatment of HCT-116 bearing nude mice with DA significantly retarded the growth of xenografts. Consistent with the results in vitro, the DA-mediated suppression of HCT-116 xenografts correlated with Bax and Bcl-2. Taken together, these results suggest that DA could be a novel and promising approach to the treatment of CRC.
authors.affiliation: Key Laboratory of Birth Defects and Obstetric & Gynecologic and Pediatric Disease of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Pharmacology, School of Pharmacy, Ningxia Medical University, Yinchuan, 750004, Ningxia, China.
authors.forename: Shaoju
authors.initials: S
authors.lastname: Jin
authors.affiliation: Department of Radiology, West China University Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Jun
authors.initials: J
authors.lastname: He
authors.affiliation: Key Laboratory of Birth Defects and Obstetric & Gynecologic and Pediatric Disease of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Zhenjun
authors.initials: Z
authors.lastname: Shao
authors.affiliation: Chengdu General Military Hospital, Chengdu, 610083, Sichuan, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Yan
authors.affiliation: Key Laboratory of Birth Defects and Obstetric & Gynecologic and Pediatric Disease of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Feng
authors.affiliation: Key Laboratory of Birth Defects and Obstetric & Gynecologic and Pediatric Disease of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009285:Naphthoquinones / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; C000595707:BCL2 protein, human; C494811:BCL2L1 protein, human; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D009285:Naphthoquinones; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C032573:beta, beta-dimethylacrylshikonin