Curcumin Induces Cross-Regulation Between Autophagy and Apoptosis in Uterine Leiomyosarcoma Cells
Curcumin Induces Cross-Regulation Between Autophagy and Apoptosis in Uterine Leiomyosarcoma Cells
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DOI：
10.1097/igc.0b013e31828c9581
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发表时间：
2013-06-01
影响因子：
4.8
通讯作者：
Yaegashi, Nobuo
中科院分区：
文献类型：
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作者：
Li, Bin;Takeda, Takashi;Yaegashi, Nobuo
目的：子宫平滑肌肉瘤（LMS）对标准化疗反应不佳。姜黄素是一种天然化合物，已被证明对癌症具有抑制作用。我们之前证明姜黄素通过靶向 AKT-mTOR 通路并激活细胞凋亡来减少子宫 LMS 细胞增殖。为了进一步探讨姜黄素的抗癌作用，我们研究了姜黄素对 LMS 细胞自噬的功效。方法：在暴露于雷帕霉素或姜黄素后评估人子宫 LMS 细胞系 SKN 和 SK-UT-1 的细胞增殖。通过蛋白质印迹法检测自噬轻链 3 和隔离体 1 (SQSTM1/p62) 的表达。通过裂解聚（ADP-核糖）聚合酶（PARP）的蛋白质印迹证实细胞凋亡。结果：雷帕霉素和姜黄素均以剂量依赖性方式有效抑制 SKN 和 SK-UT-1 细胞增殖。姜黄素可诱导 SKN 和 SK-UT-1 细胞的自噬和细胞凋亡，而特定 mTOR 抑制剂雷帕霉素则不会。姜黄素增加 SKN 和 SK-UT-1 细胞中细胞外信号调节激酶 1/2 的活性，而 MEK1 抑制剂 PD98059 抑制细胞外信号调节激酶 1/2 通路和姜黄素诱导的自噬。 结论：这些实验结果表明姜黄素是子宫 LMS 细胞增殖的有效抑制剂 并提供有关持续信号事件的新见解，从而可能开发出新的治疗剂。
Objective: Uterine leiomyosarcoma (LMS) has an unfavorable response to standard chemotherapy. A natural occurring compound, curcumin, has been shown to have inhibitory effects on cancers. We previously demonstrated that curcumin reduced uterine LMS cell proliferation by targeting the AKT-mTOR pathway and activating apoptosis. To further explore the anticancer effect of curcumin, we investigated the efficacy of curcumin on autophagy in LMS cells.Methods: Cell proliferation in human uterine LMS cell lines, SKN and SK-UT-1, was assessed after exposure to rapamycin or curcumin. Autophagy was detected by Western blotting for light chain 3 and sequestosome 1 (SQSTM1/p62) expression. Apoptosis was confirmed by Western blotting for cleaved poly (ADP-ribose) polymerase (PARP).Results: Both rapamycin and curcumin potently inhibited SKN and SK-UT-1 cell proliferation in a dose-dependent manner. Curcumin induced autophagy and apoptosis in SKN and SK-UT-1 cells, whereas rapamycin, a specific mTOR inhibitor, did not. Curcumin increased extracellular signal-regulated kinase 1/2 activity in both SKN and SK-UT-1 cells, whereas PD98059, an MEK1 inhibitor, inhibited both the extracellular signal-regulated kinase 1/2 pathway and curcumin-induced autophagy.Conclusions: These experimental findings suggest that curcumin is a potent inhibitor of cell proliferation in uterine LMS and provide new insights about ongoing signaling events leading to the possible development of a new therapeutic agent.