title: Anti-proliferative and apoptosis-inducible activity of Sarcodonin G from Sarcodon scabrosus in HeLa cells.
abstract: There is an ongoing search for plant-derived diterpenes, especially for diterpenes with anti-inflammatory activity that also have anti-proliferative effects on human cancer cells. A cyathane-type diterpene, Sarcodonin G (SG), isolated from the mushroom Sarcodon scabrosus and already reported to have anti-inflammatory activity, inhibited proliferation of HeLa cells to the greatest extent among 4 cyathane diterpenes tested. SG showed an IC50 (50% inhibition concentration) of 20 microM, estimated by MTT assay 2 days after culture of cells with the chemical. SG treatment of HeLa cells resulted in dose-dependent generation of apoptotic events such as DNA-laddering (< or =100 microM). Moreover, SG-treated HeLa cells showed activation of caspase-3 and caspase-9 and increase of Bax/Bcl-2 ratios, as analyzed by Western blot analysis. The anti-proliferative effects of SG treatment on HeLa cells were lessened by a caspase inhibitor, Z-VAD-FMK. SG also showed anti-proliferative effects toward 5 other human cancer cell lines with IC50 values of 20-40 microM. Because of these anti-proliferative effects via possible caspase activation, SG holds promise of being a novel anti-proliferative agent deserving further investigation.
authors.affiliation: Department of Medicinal Natural Product Chemistry, School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang 050017, P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Dong
authors.forename: Shi-Ping
authors.initials: SP
authors.lastname: Chen
authors.forename: Kazuko
authors.initials: K
authors.lastname: Kita
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Ichimura
authors.forename: Wen-Zhi
authors.initials: WZ
authors.lastname: Guo
authors.forename: Sa
authors.initials: S
authors.lastname: Lu
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sugaya
authors.forename: Takaki
authors.initials: T
authors.lastname: Hiwasa
authors.forename: Masaki
authors.initials: M
authors.lastname: Takiguchi
authors.forename: Naomi
authors.initials: N
authors.lastname: Mori
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kashima
authors.forename: Keiji
authors.initials: K
authors.lastname: Morimura
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Hirota
authors.forename: Nobuo
authors.initials: N
authors.lastname: Suzuki
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001487:Basidiomycota; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004224:Diterpenes / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D004224:Diterpenes; D004791:Enzyme Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C410409:sarcodonin G; D053148:Caspase 3; D053453:Caspase 9