Xu Ye, Xie Qi, Wu Shaohua, Yi Dan, Yu Yang, Liu Shibing, Li Songyan, Li Zhixin
Medical Research Laboratory, Jilin Medical University, Changchun, Jilin 132013, P.R. China.
Department of Pathophysiology, Basic Medical College, Jilin University, Changchun, Jilin 130021, P.R. China.
Mol Med Rep. 2016 Mar;13(3):2094-100. doi: 10.3892/mmr.2016.4763. Epub 2016 Jan 12.
The mechanisms underlying myricetin-induced cancer cell apoptosis remain to be elucidated. Certain previous studies have shown that myricetin induces apoptosis through the mitochondrial pathway. Apoptosis, however, can also be induced by other classical pathways, including endoplasmic reticulum (ER) stress and DNA double‑strand breaks (DSBs). The aim of the present study was to assess whether these two apoptotic pathways are involved in myricetin‑induced cell death in SKOV3 ovarian cancer cells. The results revealed that treatment with myricetin inhibited viability of SKOV3 cells in a dose‑dependent manner. Myricetin induced nuclear chromatin condensation and fragmentation, and also upregulated the protein levels of active caspase 3 in a time‑dependent manner. In addition, myricetin upregulated ER stress‑associated proteins, glucose‑regulated protein‑78 and C/EBP homologous protein in SKOV3 cells. Phosphorylation of H2AX, a marker of DNA DSBs, was revealed to be upregulated in myricetin-treated cells. The data indicated that myricetin induces DNA DSBs and ER stress, which leads to apoptosis in SKOV3 cells.
杨梅素诱导癌细胞凋亡的潜在机制仍有待阐明。此前的一些研究表明，杨梅素通过线粒体途径诱导凋亡。然而，凋亡也可由其他经典途径诱导，包括内质网（ER）应激和DNA双链断裂（DSB）。本研究的目的是评估这两种凋亡途径是否参与杨梅素诱导的SKOV3卵巢癌细胞死亡。结果显示，杨梅素处理以剂量依赖的方式抑制SKOV3细胞的活力。杨梅素诱导核染色质浓缩和碎片化，并以时间依赖的方式上调活性半胱天冬酶3的蛋白水平。此外，杨梅素上调SKOV3细胞中内质网应激相关蛋白、葡萄糖调节蛋白78和C/EBP同源蛋白。在经杨梅素处理的细胞中，DNA双链断裂的标志物H2AX的磷酸化被发现上调。数据表明，杨梅素诱导DNA双链断裂和内质网应激，从而导致SKOV3细胞凋亡。
