Cytotoxicity of the Hinokitiol-Related Compounds, γ-Thujaplicin and β-Dolabrin

• Published in: Biological & pharmaceutical bulletin Vol. 24; no. 3; pp. 299 - 302
• Main Authors: MATSUMURA, Eiko, MORITA, Yasuhiro, DATE, Tomomi, TSUJIBO, Hiroshi, YASUDA, Masahide, OKABE, Toshihiro, ISHIDA, Nakao, INAMORI, Yoshihiko
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 2001; Maruzen
• Subjects: Animals; Antineoplastic agents; Antineoplastic Agents, Phytogenic - pharmacology; Antineoplastic Agents, Phytogenic - toxicity; Biological and medical sciences; Body Weight - drug effects; Carcinoma, Ehrlich Tumor - pathology; Chemotherapy; Cycloheptanes - pharmacology; Cycloheptanes - toxicity; cytotoxic effect; Drug Screening Assays, Antitumor; Ehrlich’s ascites carcinoma; General pharmacology; hinokitiol; human stomach cancer KATO-III; Humans; Lethal Dose 50; Male; Medical sciences; Mice; Monoterpenes; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Stomach Neoplasms - pathology; Tropolone - analogs & derivatives; Tropolone - pharmacology; Tropolone - toxicity; Tumor Cells, Cultured; β-dolabrin; γ-thujaplicin; Antineoplastic agent; Pharmacognosy; Toxicity; Acute; Rodentia; Cytotoxicity; In vitro; Biological activity; Medicinal plant; Lethal dose; In vivo; Vertebrata; Mammalia; Mouse; Animal; Established cell line; Plant origin; Chelation; Mechanism of action; Tumor cell
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.24.299

γ-Thujaplicin and β-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. γ-Thujaplicin and β-dolabrin at 0.32 μg/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 γ-thujaplicin was slightly more potent than that of β-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 γ-thujaplicin and β-dolabrin in mice were 277 mg/kg and 232 mg/kg, respectively.