title: Antitumor effect of orlistat, a fatty acid synthase inhibitor, is via activation of caspase-3 on human colorectal carcinoma-bearing animal.
abstract: We established a HT-29/tk-luc human colorectal carcinoma-bearing animal model for the study of the inhibition effect and mechanism of orlistat, a fatty acid synthase (FASN) inhibitor. The results showed that orlistat caused cell cycle arrest at G1 phase, and triggered apoptosis through caspase-3 activation. The tumor inhibition effect of orlistat may also due to the inhibition of fatty acid synthesis without altering FASN activity. The tumor size of orlistat-treated mice in vivo was significantly smaller than that of the controls with 55% inhibition. The therapeutic efficacy was further confirmed with the bioluminescent imaging and nuclear molecular imaging with ¹³¹I-FIAU/gamma scintigraphy and ¹¹C-acetate/microPET. We suggest that FASN is a potential target for the treatment of human colorectal carcinoma.
authors: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, No. 155, Sec. 2, Li-Nong St., Beitou, Taipei 112, Taiwan.
authors: Hui-Yen
authors: HY
authors: Chuang
authors: Ya-Fang
authors: YF
authors: Chang
authors: Jeng-Jong
authors: JJ
authors: Hwang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003001:Cloning, Molecular; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors*; D005434:Flow Cytometry; D017930:Genes, Reporter; D018259:Herpesvirus 1, Human / Q000201:enzymology; D006801:Humans; D007783:Lactones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008163:Luminescent Measurements; D051379:Mice; D000077403:Orlistat; D013937:Thymidine Kinase / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D007783:Lactones; D000077403:Orlistat; D064429:Fatty Acid Synthases; D013937:Thymidine Kinase; D053148:Caspase 3