title: Kurarinone Synergizes TRAIL-Induced Apoptosis in Gastric Cancer Cells.
abstract: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been identified as a promising anti-tumor agent against in a variety of cancers. However, gastric cancer cells are less sensitive than other cancer cells to TRAIL-induced apoptosis. Here, we combined TRAIL with kurarinone, a natural compound, to induce apoptosis in gastric cancer cell lines SGC7901. After the cells were treated with TRAIL and/or kurarinone, the cell viability and apoptosis were examined by MTT and flow cytometry, respectively. The expression of apoptosis-associated proteins was determined by western blot and q-RT-PCR. Kurarinone at low concentration significantly potentiated the cytotoxic effect of TRAIL by enhancing apoptosis as well as cell cycle arrest at G2/Mphase. The enhancement of apoptosis TRAIL induced by kurarinone involved downregulation of anti-apoptotic proteins Mcl-1 and c-FLIP as well as inhibition of STAT3 signaling. Moreover, we found that STAT3 inhibitor could synergistically enhanced TRAIL-induced apoptosis, similar to kurarinone. Kurarinone synergizes TRAIL-induced apoptosis in human gastric cancer cells. The synergistic effect between these two drugs is associated with downregulation of Mcl-1 and c-FLIP via inhibiting STAT3 signaling. The combination of TRAIL and kurarinone might be an effective regimen for the treatment of advanced gastric cancer.
authors.affiliation: Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.|Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China.
authors.forename: Wenchao
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China.
authors.forename: Aili
authors.initials: A
authors.lastname: Cao
authors.affiliation: Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. drdazhengwu@163.com.
authors.forename: Dazheng
authors.initials: D
authors.lastname: Wu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry; D017209:Apoptosis; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000378:metabolism; D002453:Cell Cycle; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000737:chemistry*; D005434:Flow Cytometry; D006801:Humans; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000473:pathology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D005419:Flavonoids; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C411319:kurarinone
keywords: Apoptosis; Gastric cancer; Kurarinone; STAT3; TRAIL