Up-regulation of Death Receptor 5/TRAIL-R2 Mediates Apoptosis Induced by N,N'-[(3,4-dimethoxyphenyl)methylene] Biscinnamide in Cancer Cells.
BACKGROUND/AIM
Based on the cytotoxic agent (-)-zampanolide, N,N'-(arylmethylene)bisamides were designed and synthesized as candidate anti-cancer agents. Among them, N,N'-[(3,4-dimethoxyphenyl)methylene]biscinnamide (DPMBC) was identified as the most potent cytotoxic analog against cancer cells. In this study, we investigated the mechanisms underlying DPMBC-induced cell death in HL-60 human promyelocytic leukemia and PC-3 human prostate cancer cells.


MATERIALS AND METHODS
Cell growth was assessed by the WST-8 assay. Induction of apoptosis was assessed by nuclear morphology, DNA ladder formation, and flow cytometry using Annexin V staining. Activation of factors in the apoptotic signaling pathway was assessed by western blot analyses. Knockdown of death receptor 5 (DR5) was performed using siRNA.


RESULTS
DPMBC up-regulated expression levels of DR5 protein and induced apoptosis through the extrinsic apoptotic pathway mediated by DR5 and caspases.


CONCLUSION
DPMBC is an extrinsic apoptosis inducer, which has potential as a therapeutic agent for cancer therapy.
['Hiromi|Ii|I|', 'Nakata|Susumu|S|', "Uenishi|Jun'ichi|J|"]
D000970:Antineoplastic Agents D017209:Apoptosis D020169:Caspases D045744:Cell Line, Tumor D049109:Cell Proliferation D053938:DNA Fragmentation D004305:Dose-Response Relationship, Drug D015972:Gene Expression Regulation, Neoplastic D006801:Humans D018942:Macrolides D015394:Molecular Structure D034741:RNA, Small Interfering D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand
death receptor 5 apoptosis cancer cells caspase N,N’-(arylmethylene)biscinnamide