PT - JOURNAL ARTICLE AU - HIROMI II AU - SUSUMU NAKATA AU - JUN'ICHI UENISHI TI - Up-regulation of Death Receptor 5/TRAIL-R2 Mediates Apoptosis Induced by <em>N,Nā€™</em>-[(3,4-dimethoxyphenyl)methylene] Biscinnamide in Cancer Cells AID - 10.21873/anticanres.14506 DP - 2020 Sep 01 TA - Anticancer Research PG - 5035--5041 VI - 40 IP - 9 4099 - http://ar.iiarjournals.org/content/40/9/5035.short 4100 - http://ar.iiarjournals.org/content/40/9/5035.full SO - Anticancer Res2020 Sep 01; 40 AB - Background/Aim: Based on the cytotoxic agent (āˆ’)-zampanolide, N,Nā€™-(arylmethylene)bisamides were designed and synthesized as candidate anti-cancer agents. Among them, N,Nā€™-[(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.