CUDC-907 enhances TRAIL-induced apoptosis through upregulation of DR5 in breast cancer cells
CUDC-907 enhances TRAIL-induced apoptosis through upregulation of DR5 in breast cancer cells
复制标题
CUDC-907 通过上调乳腺癌细胞中 DR5 增强 TRAIL 诱导的细胞凋亡
DOI：
10.1007/s12079-020-00558-3
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发表时间：
2020-03-21
影响因子：
4.1
通讯作者：
Wang, Feng-Ze
中科院分区：
文献类型：
--
作者：
Li, Zhao-Jun;Hou, Ya-Jun;Wang, Feng-Ze
CUDC-907 is a novel dual-acting inhibitor of phosphoinositide 3-kinase (PI3K) and histone deacetylase (HDAC). In this study, we aimed to explore the anticancer effects of CUDC-907 on human breast cancer cells. Our results showed that CUDC-907 effectively inhibited breast cancer cell proliferation. Flow cytometry analysis revealed that CUDC-907 induced cell cycle arrest and apoptosis in breast cancer cells. The combined treatment of CUDC-907 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resulted in a marked increase in apoptosis and cleavage of caspase-8, -9 and poly (ADP-ribose) polymerase (PARP) in breast cancer cells. CUDC-907 enhanced expressions of death receptor 5 (DR5), reduced the levels of anti-apoptotic molecules XIAP, Bcl-2 and Bcl-xL. Knockdown of DR5 abrogated apoptosis induced by the combination of CUDC-907 and TRAIL in breast cancer cells. CUDC-907 increased the phosphorylation of JNK and p38 MAPK. JNK inhibitor pretreatment attenuated CUDC-907-induced upregulation of DR5. In summary, CUDC-907 shows potent cytotoxicity against breast cancer cells and facilitates TRAIL-mediated apoptosis through DR5 upregulation. The combination of CUDC-907 and TRAIL may be a promising therapeutic approach in the treatment of breast cancer.
