Synergistic Induction of Apoptosis by Quercetin and Curcumin in Chronic Myeloid Leukemia (K562) Cells
Synergistic Induction of Apoptosis by Quercetin and Curcumin in Chronic Myeloid Leukemia (K562) Cells
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DOI：
10.1080/01635581.2018.1380208
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发表时间：
2018-01-01
影响因子：
2.9
通讯作者：
Yalcin, A. Suha
中科院分区：
文献类型：
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作者：
Altundag, Ergul Mutlu;Yilmaz, Ayse Mine;Yalcin, A. Suha
慢性粒细胞白血病是一种主要的造血系统恶性肿瘤，其特征是骨髓细胞的扩增。本研究探讨了槲皮素、姜黄素及其联合应用是否能诱导K562细胞凋亡并抑制其生长。我们已经观察到槲皮素和姜黄素组合诱导细胞凋亡，伴随着增加的ROS和降低的GSH水平以及线粒体膜电位的损失。我们的mRNA和蛋白表达结果表明，细胞色素c从线粒体释放，引起PARP和caspase-9裂解，线粒体凋亡途径的标志。我们认为，细胞凋亡的触发主要是通过线粒体途径，ROS的产生可能导致线粒体膜电位的损害。槲皮素和姜黄素组合的使用增强多酚的个体凋亡作用并降低其有效剂量，从而防止对正常细胞的潜在毒性作用。当然需要额外的临床前研究和临床试验来进一步验证它们作为有效抗癌剂的有用性。
Chronic myeloid leukemia is a major hematopoietic malignancy characterized by expansion of myeloid cells. In this study, we have investigated whether quercetin, curcumin and their combination induce apoptosis and inhibit growth of K562 cells. We have observed that quercetin and curcumin combination induced apoptosis accompanied by increased ROS and decreased GSH levels as well as loss of mitochondrial membrane potential. Our mRNA and protein expression results suggested that cytochrome c was released from mitochondria causing PARP and caspase-9 cleavages, the hallmarks of mitochondrial apoptotic pathway. We believe that triggering of apoptosis is mostly via mitochondrial pathway and ROS generation may induce impairment of mitochondrial membrane potential. The use of quercetin and curcumin combination potentiates individual apoptotic effects of the polyphenols and reduces their effective dose thereby preventing potential toxic effects on normal cells. Additional preclinical studies and clinical trials are certainly required to further validate their usefulness as potent anticancer agents.