Cytotoxicity of the hinokitiol-related compounds, gamma-thujaplicin and beta-dolabrin.
Gamma-thujaplicin and beta-dolabrin, the constituents of the wood of Thujopsis dolabrata Sieb. et Zucc. var. hondai showed strong in vitro cytotoxic effects against the human stomach cancer cell lines KATO-III and Ehrlich's ascites carcinoma. The cytotoxic effects of the two compounds against both tumor cell lines were clear when cell growth was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Gamma-thujaplicin and beta-dolabrin at 0.32 microg/ml inhibited cell growth of human stomach cancer KATO-III by 85 and 67%, and Ehrlich's ascites carcinoma by 91 and 75%, respectively. There is no large difference in cytotoxicity between these compounds, but the activity of gamma-thujaplicin was slightly more potent than that of beta-dolabrin. On the other hand, hinokitiol acetate did not show a cytotoxic effect, suggesting that at least a part of the mechanism of the cytotoxic effect of hinokitiol-related compounds is due to metal chelation between the carbonyl group at C-1 and the hydroxyl group at C-2 in the tropolone skeleton of these molecules. The acute toxicities [50% lethal dose (LD50) value: intraperitoneal injection, Van der Waedem] of gamma-thujaplicin and beta-dolabrin in mice were 277 mg/kg and 232 mg/kg, respectively.
Osaka University of Pharmaceutical Sciences, Japan.
E
E
Matsumura
Y
Y
Morita
T
T
Date
H
H
Tsujibo
M
M
Yasuda
T
T
Okabe
N
N
Ishida
Y
Y
Inamori
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000633:toxicity; D001835:Body Weight / Q000187:drug effects; D002286:Carcinoma, Ehrlich Tumor / Q000473:pathology; D003508:Cycloheptanes / Q000494:pharmacology* / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D039821:Monoterpenes; D013274:Stomach Neoplasms / Q000473:pathology; D014334:Tropolone / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000633:toxicity; D014407:Tumor Cells, Cultured
C116333:2-hydroxy-5-isopropyl- 2,4,6-cycloheptatrienone; D000972:Antineoplastic Agents, Phytogenic; D003508:Cycloheptanes; D039821:Monoterpenes; C410956:beta-dolabrin; D014334:Tropolone; C009479:beta-thujaplicin