title: The anticancer effect of chaetocin is enhanced by inhibition of autophagy.
abstract: Chaetocin is a fungal metabolite that possesses a potent antiproliferative activity in solid tumors by inducing cell death. Although recent studies have extended the role of chaetocin in tumors, the underlying molecular mechanisms such as the downstream cascade that induces cell death has not clearly been elucidated. In this study, we show that chaetocin is able to induce both apoptosis and autophagy in several hepatoma cell lines including HepG2, Hep3B and Huh7 cell lines. Moreover, we found that the inhibition of caspase-3/7 activity by z-VAD-fmk treatment was able to block chaetocin-mediated cell death, whereas blocking autophagy by Bafilomycin A1 or the knockdown of autophagy protein 5 enhanced cell death mediated by chaetocin. These findings suggest that chaetocin has a potent anticancer effect against hepatoma. Inhibition of autophagy may potentiate anticancer effects of chaetocin thus providing evidence that combined treatment with chaetocin and autophagy inhibitors will be an effective strategy for treating cancer.
authors.affiliation: Department of Microbiology, School of Medicine, Keimyung University, Daegu, Republic of Korea.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Jung
authors.affiliation: Department of Microbiology, School of Medicine, Keimyung University, Daegu, Republic of Korea.
authors.forename: I
authors.initials: I
authors.lastname: Seo
authors.affiliation: Control of Gene Expression Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
authors.forename: F
authors.initials: F
authors.lastname: Casciello
authors.affiliation: Division of Immunology, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Jacquelin
authors.affiliation: Division of Immunology, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
authors.forename: S W
authors.initials: SW
authors.lastname: Lane
authors.affiliation: Department of Microbiology, School of Medicine, Keimyung University, Daegu, Republic of Korea.
authors.forename: S-Il
authors.initials: SI
authors.lastname: Suh
authors.affiliation: Department of Microbiology, School of Medicine, Keimyung University, Daegu, Republic of Korea.
authors.forename: M-H
authors.initials: MH
authors.lastname: Suh
authors.affiliation: Control of Gene Expression Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
authors.forename: J S
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Microbiology, School of Medicine, Keimyung University, Daegu, Republic of Korea.|Institute for Cancer Research, Keimyung University, Daegu, Republic of Korea.
authors.forename: W-K
authors.initials: WK
authors.lastname: Baek
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D010879:Piperazines / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D010879:Piperazines; C002511:chaetocin