Nomura Masaaki, Takahashi Tatsuo, Uesugi Aimi, Tanaka Reiko, Kobayashi Shinjiro
Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Ishikawa 920-1181, Japan.
Anticancer Res. 2008 Sep-Oct;28(5A):2691-6.
To investigate the antitumor effect of Inonotus obliquus Pilat, the antiproliferative effect of lanostane triterpenoids from a chloroform extract of I. obliquus sclerotia against mouse leukemia P388 cells was assessed.
Cell viability was measured by MTT assay. Caspase-3/7 activity and DNA fragmentation were evaluated to analyze apoptosis induction. The in vivo antitumor effect was evaluated by the number of survival days of mouse leukemia P388-bearing female CDF1 mice.
The chloroform extract of I. obliquus sclerotia inhibited proliferation of the P388 cells. Among the triterpenoids examined, only inotodiol inhibited P388 cell proliferation. DNA fragmentation and caspase-3/7 activation were observed in the P388 cells treated with inotodiol (30 microM). A caspase-3 inhibitor, DEVD-CHO (N-acetyl-Asp-Glu-Val-Asp-al, 100 microM) partially inhibited the DNA fragmentation and growth-inhibition induced by inotodiol. The intraperitoneal administration of 10 mg/kg inotodiol prolonged the number of survival days of the P388-bearing mice.
Inotodiol inhibits cell proliferation through apoptosis induction by activating caspase-3.
为研究桦褐孔菌的抗肿瘤作用，评估了桦褐孔菌菌核氯仿提取物中羊毛甾烷三萜类化合物对小鼠白血病P388细胞的抗增殖作用。
采用MTT法测定细胞活力。通过评估半胱天冬酶-3/7活性和DNA片段化来分析凋亡诱导情况。通过荷小鼠白血病P388的雌性CDF1小鼠的存活天数评估体内抗肿瘤作用。
桦褐孔菌菌核氯仿提取物抑制P388细胞增殖。在所检测的三萜类化合物中，只有氧化三萜二醇抑制P388细胞增殖。在用氧化三萜二醇（30微摩尔）处理的P388细胞中观察到DNA片段化和半胱天冬酶-3/7激活。半胱天冬酶-3抑制剂DEVD-CHO（N-乙酰天冬氨酸-谷氨酸-缬氨酸-天冬氨酸醛，100微摩尔）部分抑制了氧化三萜二醇诱导的DNA片段化和生长抑制。腹腔注射10毫克/千克氧化三萜二醇可延长荷P388小鼠的存活天数。
氧化三萜二醇通过激活半胱天冬酶-3诱导凋亡来抑制细胞增殖。
