Hybrid Benzoxazole-Coumarin Compounds Induce Death Receptor-Mediated Switchable Apoptotic and Necroptotic Cell Death on Hn-5 Head and Neck Cancer Cell Line Publisher Pubmed



Yaghmaei S¹ ; Ghalayani P¹ ; Salami S² ; Nourmohammadian F³ ; Soheila K² ; Vahideh I² Show Affiliations
Source: Anti-Cancer Agents in Medicinal Chemistry Published:2016

Abstract

Background: Efficacy of multimodality approaches for the treatment of squamous cell cancer of the head and neck has remained unsatisfactory and further advances are critically required. Targeted cell death induction is a novel therapeutic approach that may help to improve clinical management of Head and Neck cancer patients. Objective: The potency of novel hybrid benzoxazole-coumarins on the induction of apoptotic and/or necroptotic cell death were evaluated in a Head and Neck carcinoma cell line, HN-5, and a human skin cell line, AGO1522. Methods: Quantitative toxicity of the synthesized compounds were elucidated by MTT assay, the specific activity of caspase-3 and -9 were measured by the colorimetric method and zVAD was used to block apoptosis. Expression of cell death related genes were studied using quantitative PCR. Results: All three compounds revealed IC50 value M in HN-5 cells which were significaμaround 51.96±7.15 ntly lower than observed M(p=0.001). Significant increase expression of μIC50 for AGO1522, 121.93±3.66 FAS, FASL and TRIAL were observed in the treated cells with or without pretreatment with zVAD. In the absence of pretreatment, treatment lead to the induction of apoptosis with a significant increase in caspase-3 gene expression and caspase-3 activity without a significant increase in expression or activity of caspase-9 and other components of the intrinsic apoptotic pathway. However, in the zVAD pretreated cells, necroptotic cell death with a significant increase in expression of RIP1, RIP3, and MLKL genes was observed Conclusion: The novel hybrid benzoxazole-coumarins effectively induce caspase 3 dependent apoptosis in HN-5 cancer cells, but also could circumvent the blockage of apoptotic cell death by induction of necroptosis. © 2016 Bentham Science Publishers.