Farnesyltransferase inhibitors-induced autophagy Alternative mechanisms?
Farnesyltransferase inhibitors-induced autophagy Alternative mechanisms?
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DOI：
10.4161/auto.5.1.7329
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发表时间：
2009-01-01
期刊：
影响因子：
13.3
通讯作者：
Yeung, Sai-Ching Jim
中科院分区：
文献类型：
--
作者：
Pan, Jingxuan;Song, Enlin;Yeung, Sai-Ching Jim
法尼基转移酶抑制剂（FTIs）通过添加法尼基类异戊二烯膜锚来阻断依赖于翻译后修饰的Ras癌蛋白的作用。然而，脱靶作用被认为是其大部分抗肿瘤活性的原因。我们最近报道了FTIs以剂量依赖性方式诱导癌细胞自噬。我们在一组肿瘤细胞系中观察到了三种测试的FTI的自噬类似结果。因此，自噬的诱导很可能是法尼基转移酶抑制的药理学类效应。在本附录中，我们讨论了FTI诱导自噬的可能机制，包括活性氧自由基、DNA损伤和Ras介导的途径，作为Rheb介导的mTOR和自噬调节的替代方案。
Farnesyltransferase inhibitors (FTIs) were designed to block the action of Ras oncoproteins which depend on posttranslational modification by adding a farnesyl isoprenoid membrane anchor. However, off-target actions are believed to account for most of their antitumor activity. We recently reported the induction of autophagy in cancer cells in a dose-dependent manner by FTIs. We observed similar results of autophagy in a panel of tumor cell lines for the three FTIs tested. Therefore, the induction of autophagy is very likely a pharmacological class effect of inhibition of farnesyltransferase. In this addendum, we discuss the possible mechanisms underlying the induction of autophagy by FTIs, including reactive oxygen species-, DNA damage- and Ras-mediated pathways as alternatives to Rheb-mediated regulation of mTOR and autophagy.