Open AccessCUDC‐907 enhances TRAIL‐induced apoptosis through upregulation of DR5 in breast cancer cells
Author(s) -
Li ZhaoJun,
Hou YaJun,
Hao GangPing,
Pan XiaoXuan,
Fei HongRong,
Wang FengZe
Publication year - 2020
Publication title -
journal of cell communication and signaling
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 44
eISSN - 1873-961X
pISSN - 1873-9601
DOI - 10.1007/s12079-020-00558-3
Subject(s) - downregulation and upregulation , apoptosis , breast cancer , cancer research , medicine , cancer , bioinformatics , biology , gene , biochemistry
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.