Anti-proliferative and apoptosis-inducible activity of Sarcodonin G from Sarcodon scabrosus in HeLa cells.
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.
Dong
Mei
M
Department of Medicinal Natural Product Chemistry, School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang 050017, P.R. China.
Chen
Shi-Ping
SP
Kita
Kazuko
K
Ichimura
Yoshinobu
Y
Guo
Wen-Zhi
WZ
Lu
Sa
S
Sugaya
Shigeru
S
Hiwasa
Takaki
T
Takiguchi
Masaki
M
Mori
Naomi
N
Kashima
Atsushi
A
Morimura
Keiji
K
Hirota
Mitsuru
M
Suzuki
Nobuo
N
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
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