Department of Pharmacology, Center for Gene Regulation and Signal Transduction Research, National Cheng-Kung University, Tainan, Taiwan.
Autophagy. 2011 Feb;7(2):166-75. doi: 10.4161/auto.7.2.14043. Epub 2011 Feb 1.
Minocycline has been shown to alleviate several neurological disorders. Unexpectedly, we found that minocycline had opposite effects on glioma cells: minocycline induced nonapoptotic cell death in glioma cells. The glioma cell death was associated with the presence of autophagic vacuoles in the cytoplasm. Minocycline induced autophagy was confirmed by acridine orange, monodansylcadaverine (MDC) stainings of vesicle formation and the conversion of microtubule-associated proteins light chain 3 (LC3-I) to LC3-II. Pretreatment with autophagy inhibitor 3-methyladenine (3-MA) suppressed the induction of acidic vesicular organelles and the accumulation of LC3-II to the autophagosome membrane in glioma cells treated with minocycline. Despite the pretreatment of 3-MA, minocycline induced cell death which could result from the activation of caspase-3. Minocycline effectively inhibited tumor growth and induced autophagy in the xenograft tumor model of C6 glioma cells. These results suggest that minocycline may kill glioma cells by inducing autophagic cell death. When autophagy was inhibited, minocycline still induced cell death through the activation of caspase-3. Thus, minocycline is a promising agent in the treatment of malignant gliomas.
米诺环素已被证明能缓解多种神经紊乱。出人意料的是，我们发现米诺环素对神经胶质瘤细胞有相反的作用：米诺环素诱导神经胶质瘤细胞发生非凋亡性细胞死亡。这种神经胶质瘤细胞死亡与细胞质中自噬空泡的存在有关。米诺环素诱导的自噬通过吖啶橙、单丹磺酰戊二胺（MDC）染色证实了囊泡形成和微管相关蛋白轻链 3（LC3-I）向 LC3-II 的转化。自噬抑制剂 3-甲基腺嘌呤（3-MA）预处理可抑制米诺环素处理的神经胶质瘤细胞中酸性囊泡细胞器的诱导和 LC3-II 向自噬体膜的积累。尽管进行了 3-MA 预处理，米诺环素仍能诱导细胞死亡，这可能是由于 caspase-3 的激活。米诺环素能有效抑制 C6 神经胶质瘤细胞移植瘤模型中的肿瘤生长并诱导自噬。这些结果表明，米诺环素可能通过诱导自噬性细胞死亡来杀死神经胶质瘤细胞。当自噬被抑制时，米诺环素仍通过 caspase-3 的激活诱导细胞死亡。因此，米诺环素是治疗恶性神经胶质瘤的一种有前途的药物。
