title: Enhanced antitumor activity of cerulenin combined with oxaliplatin in human colon cancer cells.
abstract: Fatty acid synthase is highly expressed in many types of human cancers. Cerulenin, a natural inhibitor of fatty acid synthase, induced apoptosis in the human colon cancer cell lines HCT116 and RKO. Oxaliplatin also induced cell death in these cell lines. Cerulenin treatment was associated with reduced levels of phosphorylated Akt, activation of p38 and induced caspase-3 cleavage and finally caused apoptosis. Oxaliplatin induced activation of the p53-p21 pathway and p38. In combination with cerulenin and oxaliplatin, activation of the p53-p21 pathway and p38 occurred in a smaller concentration and finally induced caspase-3 cleavage in a smaller concentration of cerulenin and oxaliplatin. In xenotransplanted SCID mice, the cerulenin + oxaliplatin group significantly inhibited tumor progression compared to the control, cerulenin and oxaliplatin groups. Based on these studies, inhibiting fatty acid synthase would be an effective strategy to treat unresectable colorectal cancer tumors in combination with oxaliplatin. Fatty acid synthase inhibitor would be one of the best counterparts of oxaliplatin, which reduces the dose and side-effects of oxaliplatin and would make it possible to endure the chemotherapy over a longer period.
authors.affiliation: Department of Surgery, Teikyo University Chiba Medical Center, Ichihara, Chiba 299-0111, Japan.
authors.forename: Risa
authors.initials: R
authors.lastname: Shiragami
authors.forename: Soichiro
authors.initials: S
authors.lastname: Murata
authors.forename: Chihiro
authors.initials: C
authors.lastname: Kosugi
authors.forename: Tohru
authors.initials: T
authors.lastname: Tezuka
authors.forename: Masato
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hirano
authors.forename: Yukino
authors.initials: Y
authors.lastname: Yoshimura
authors.forename: Masato
authors.initials: M
authors.lastname: Suzuki
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Shuto
authors.forename: Keiji
authors.initials: K
authors.lastname: Koda
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D002569:Cerulenin / Q000494:pharmacology / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy*; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors; D054872:Fatty Acid Synthesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D009944:Organoplatinum Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D000077150:Oxaliplatin
chemical_list: D000970:Antineoplastic Agents; D054872:Fatty Acid Synthesis Inhibitors; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002569:Cerulenin; D064429:Fatty Acid Synthases