title: Apoptotic effect of demethoxyfumitremorgin C from marine fungus Aspergillus fumigatus on PC3 human prostate cancer cells.
abstract: Demethoxyfumitremorgin C, a secondary metabolite of the marine fungus, Aspergillus fumigatus, had been reported to demonstrate cytotoxic effect on mouse tsFT210 cells. However, no information is available regarding its functional mechanism and the chemo-sensitization effects on different kinds of human cancer cells. We found that treatment of demethoxyfumitremorgin C inhibited the cell viability of PC3 human advanced prostate cancer cells, induced apoptosis as determined by Annexin V/propidium iodide double staining, and decreased mitochondrial membrane potential. Demethoxyfumitremorgin C induced apoptosis was associated with downregulation of anti-apoptotic proteins: Ras, PI3K, Akt, Bcl-xL, and Bcl-2, and upregulation of pro-apoptotic Bax. Demethoxyfumitremorgin C activated caspase-3, -8, and -9, leading to PARP cleavage. Additionally, caspase inhibitors blocked demethoxyfumitremorgin C-induced apoptosis of PC3 cells. These results suggest that demethoxyfumitremorgin C from Aspergillus fumigatus inhibits the proliferation of PC3 human prostate cancer cells via the intrinsic (mitochondrial) and extrinsic pathway, followed by downstream events leading to apoptotic cell death. Demethoxyfumitremorgin C could therefore, serve as a useful agent to treat human advanced prostate cancer.
authors.affiliation: Department of Chemistry, Pukyong National University, Busan 608-737, Republic of Korea.
authors.forename: Young-Sang
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Institute of Life Science of Seogo, Kolmar Korea, Seoul, 137-876, Republic of Korea. Electronic address: sknkim@pknu.ac.kr.
authors.forename: Se-Kwon
authors.initials: SK
authors.lastname: Kim
authors.affiliation: Department of Chemistry, Pukyong National University, Busan 608-737, Republic of Korea. Electronic address: parksj@pknu.ac.kr.
authors.forename: Sun Joo
authors.initials: SJ
authors.lastname: Park
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001232:Aspergillus fumigatus / Q000737:chemistry* / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D018631:ras Proteins / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D010879:Piperazines; C100698:demethoxyfumitremorgin C; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D018631:ras Proteins
keywords: Apoptosis; Aspergillus fumigatus; Demethoxyfumitremorgin C; Marine fungus; Prostate cancer