Curcumin Suppresses Proliferation and Migration of MDA-MB-231 Breast Cancer Cells through Autophagy-Dependent Akt Degradation.
Curcumin Suppresses Proliferation and Migration of MDA-MB-231 Breast Cancer Cells through Autophagy-Dependent Akt Degradation.
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姜黄素通过自噬依赖性 Akt 降解抑制 MDA-MB-231 乳腺癌细胞的增殖和迁移。
DOI：
10.1371/journal.pone.0146553
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Wang C
中科院分区：
文献类型：
--
作者：
Guan F;Ding Y;Zhang Y;Zhou Y;Li M;Wang C
姜黄素（diferuloylmethane）是姜黄中的一种主要的黄色生物活性化合物，其抗癌作用是通过干扰PI 3 K/Akt信号通路来实现的。然而，其潜在的分子机制仍然知之甚少。这项研究实验表明，姜黄素处理以剂量和时间依赖性方式降低MDA-MB-231乳腺癌细胞中Akt蛋白的表达，沿着自噬的激活和泛素-蛋白酶体系统（UPS）功能的抑制。姜黄素减少Akt的表达，细胞增殖和迁移被阻止的遗传和药理学抑制自噬，但不通过UPS抑制。此外，AMPK通过其特异性抑制剂化合物C或靶向shRNA介导的沉默的失活减弱了姜黄素激活的自噬。因此，这些结果表明，姜黄素刺激的AMPK活性诱导自噬-溶酶体蛋白降解途径的激活，导致Akt降解和随后的乳腺癌细胞增殖和迁移的抑制。
Previous studies have evidenced that the anticancer potential of curcumin (diferuloylmethane), a main yellow bioactive compound from plant turmeric was mediated by interfering with PI3K/Akt signaling. However, the underlying molecular mechanism is still poorly understood. This study experimentally revealed that curcumin treatment reduced Akt protein expression in a dose- and time-dependent manner in MDA-MB-231 breast cancer cells, along with an activation of autophagy and suppression of ubiquitin-proteasome system (UPS) function. The curcumin-reduced Akt expression, cell proliferation, and migration were prevented by genetic and pharmacological inhibition of autophagy but not by UPS inhibition. Additionally, inactivation of AMPK by its specific inhibitor compound C or by target shRNA-mediated silencing attenuated curcumin-activated autophagy. Thus, these results indicate that curcumin-stimulated AMPK activity induces activation of the autophagy-lysosomal protein degradation pathway leading to Akt degradation and the subsequent suppression of proliferation and migration in breast cancer cell.