Inhibitory effects of asiatic acid and CPT-11 on growth of HT-29 cells
Inhibitory effects of asiatic acid and CPT-11 on growth of HT-29 cells
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DOI：
10.2152/jmi.52.65
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发表时间：
2005-02-01
影响因子：
0.7
通讯作者：
Ohnishi, Yoshinari
中科院分区：
文献类型：
--
作者：
Bunpo, Piyawan;Kataoka, Keiko;Ohnishi, Yoshinari
积雪草酸是药用植物中的一种五环三萜。在人结肠癌细胞系HT-29中研究了该化合物的毒性作用及其对抗癌药物盐酸伊立替康（CPT-11）的增强作用。积雪草酸对HT-29细胞的毒性呈剂量依赖性。DNA片段化、膜联蛋白阳性凋亡细胞和caspase-3激活呈剂量依赖性。半胱天冬酶-3抑制剂以浓度依赖性方式抑制DNA梯状条带的形成。积雪草酸处理降低了Bcl-2和Bcl-xL蛋白的表达。以上结果表明积雪草酸通过激活caspase-3诱导HT-29细胞凋亡。进一步观察CPT-11和积雪草酸联合作用对HT-29细胞的细胞毒作用。同时处理或顺序暴露，首先积雪草酸，然后CPT-11显示了累加效应。CPT-11和积雪草酸对细胞的协同作用明显。这些结果表明积雪草酸可作为一种药物，用于增加结肠癌细胞对CPT-11治疗的敏感性，或作为一种药物，用于减少CPT-11的副作用。
Asiatic acidis apentacyclictriterpenecontainedinmedicinalplants. Thecytotoxiceffect of this compound and its augmentative effect on the anticancer drug irinotecan hydrochloride (CPT-11) were investigated in the human colon adenocarcinoma cell lineHT-29. Asiatic acid dose-dependently showed cytotoxicity in HT-29 cells. DNA fragmentation, annexin-positive apoptotic cells, andcaspase-3 activationwere observed ina dose-dependentmanner. Acaspase-3 inhibitor suppressed the DNA ladder formation in a concentration-dependent manner. Bcl-2 and Bcl-xL proteins were decreased by asiatic acid treatment. These results indicate that asiatic acidinducedapoptosis inHT-29 cells viacaspase-3activation. Cytotoxiceffectsof combined treatment with CPT-11 and asiatic acid on HT-29 cellswere further examined. Simultaneous treatment or sequential exposure first to asiatic acid and then to CPT-11 showed an additive effect. Synergism was observedwhen cells were first exposed to CPT-11 and then to asiatic acid. These results suggest that asiatic acid can be used as an agent for increasing sensitivity of colon cancer cells to treatmentwith CPT-11 or as an agent for reducing adverse effects of CPT-11.