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.
Keywords: N,N’-(arylmethylene)biscinnamide; apoptosis; cancer cells; caspase; death receptor 5.
Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.