Hata Keishi, Hori Kazuyuki, Ogasawara Hironobu, Takahashi Saori
Akita Research Institute of Food and Brewing (ARIF), 4-26 Sanuki, Araya-Machi, Akita 010-1623, Japan.
Toxicol Lett. 2003 Jun 5;143(1):1-7. doi: 10.1016/s0378-4274(03)00092-4.
The cytotoxicities of 11 lupane series triterpenes against 3 human leukemias, 2 melanomas, 2 neuroblastomas and normal fibroblast cells were examined. Lupane triterpenes with a carbonyl group at C-17 (7-11) showed inhibitory effects on leukemia, melanoma and neuroblastoma cell growth. Lup-28-al-20(29)-en-3-one (8) markedly inhibited the cell growth of 3 leukemias to a greater extent than the other human cancers and normal lung fibroblast cells. The cytotoxicity profiles of 8 against human cancer cells showed that its cytotoxic effect against 3 lung cancer cell lines was strong and the cytotoxic effects against osteosarcoma, breast cancer and urinary bladder cancer cells were very weak. The morphological observations of leukemia nuclei and the gel electrophoresis analysis of DNA extracted from 8-treated leukemia cells revealed that 8 induced leukemia cell apoptosis. Furthermore, we investigated the cytotoxic effects of 8 on adriamycin (ADM)- and vincristine (VCR)-resistant K562 (K562/ADM and K562/VCR) cells. K562/ADM and K562/VCR cells showed greater resistance toward ADM and VCR when compared to parent K562 cells. However, 8 inhibited the drug-resistant K562 cell growth to the same extent as K562 cells by the induction of apoptosis.
检测了11种羽扇豆烷系列三萜对3种人类白血病细胞、2种黑色素瘤细胞、2种神经母细胞瘤细胞和正常成纤维细胞的细胞毒性。在C-17（7-11）位带有羰基的羽扇豆烷三萜对白血病、黑色素瘤和神经母细胞瘤细胞的生长具有抑制作用。羽扇豆-28-醛-20（29）-烯-3-酮（8）对3种白血病细胞生长的抑制作用明显强于其他人类癌细胞和正常肺成纤维细胞。8对人类癌细胞的细胞毒性谱显示，其对3种肺癌细胞系的细胞毒性作用较强，而对骨肉瘤、乳腺癌和膀胱癌细胞的细胞毒性作用非常弱。对白血病细胞核的形态学观察以及对从经8处理的白血病细胞中提取的DNA进行的凝胶电泳分析表明，8可诱导白血病细胞凋亡。此外，我们研究了8对阿霉素（ADM）和长春新碱（VCR）耐药的K562细胞（K562/ADM和K562/VCR）的细胞毒性作用。与亲本K562细胞相比，K562/ADM和K562/VCR细胞对ADM和VCR表现出更强的耐药性。然而，8通过诱导凋亡，对耐药K562细胞生长的抑制程度与K562细胞相同。
