Jia Yan-Li, Li Jun, Qin Zheng-Hong, Liang Zhong-Qin
Department of Pharmacology, Soochow University School of Medicine, Suzhou, China.
J Asian Nat Prod Res. 2009 Nov;11(11):918-28. doi: 10.1080/10286020903264077.
Curcumin (1), a natural polyphenolic compound, has shown strong antioxidant and anticancer activities. Several molecular mechanisms have been attributed to its inhibitory effects on a wide range of tumor cells. In this study, the response of the chronic myeloid leukemia cell line K562 cells to 1 is investigated. Curcumin inhibited the viability of K562 cells in a dose- and time-dependent manner. Furthermore, curcumin-induced cell death was associated with the formation of the apoptosome complex, the collapse of the mitochondrial membrane potential, and caspase-3 activation. Curcumin treatment also induced Bid cleavage and downregulated the expression of Bcl-2 protein. Surprisingly, even with these molecular features of apoptosis, we showed that 1 stimulated autophagy, which was evidenced by microtubule-associated protein light chain 3 (LC3) immunoreactivty. Curcumin also increased the protein levels of beclin 1 and membrane form LC3 (LC3-II). Autophagy inhibitor bafilomycin A1 and the pan-caspase inhibitor Z-VAD-fmk suppressed curcumin-induced K562 cell death. Overall, these results suggest that curcumin induces autophagic and apoptotic death of K562 cells. These findings suggest that both apoptotic and autophagic mechanisms contribute to the curcumin-induced K562 cell death.
姜黄素（1）是一种天然多酚化合物，已显示出强大的抗氧化和抗癌活性。其对多种肿瘤细胞的抑制作用归因于多种分子机制。在本研究中，对慢性髓性白血病细胞系K562细胞对1的反应进行了研究。姜黄素以剂量和时间依赖性方式抑制K562细胞的活力。此外，姜黄素诱导的细胞死亡与凋亡小体复合物的形成、线粒体膜电位的崩溃以及半胱天冬酶-3的激活有关。姜黄素处理还诱导Bid裂解并下调Bcl-2蛋白的表达。令人惊讶的是，即使具有这些凋亡的分子特征，我们仍表明1刺激了自噬，这通过微管相关蛋白轻链3（LC3）免疫反应性得到证实。姜黄素还增加了beclin 1和膜形式LC3（LC3-II）的蛋白水平。自噬抑制剂巴弗洛霉素A1和泛半胱天冬酶抑制剂Z-VAD-fmk抑制了姜黄素诱导的K562细胞死亡。总体而言，这些结果表明姜黄素诱导K562细胞发生自噬性和凋亡性死亡。这些发现表明，凋亡和自噬机制均促成了姜黄素诱导的K562细胞死亡。
