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Anti-Cancer Agents in Medicinal Chemistry


ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

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

Author(s): Sahar Yaghmaei, Parichehr Ghalayani, Siamak Salami*, Farahnaz Nourmohammadian, Soheila Koohestanimobarhan and Vahideh Imeni

Volume 17, Issue 4, 2017

Page: [608 - 614] Pages: 7

DOI: 10.2174/1871520616666160725110844

Price: $65


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 were revealed IC50 value around 51.96±7.15 microM in HN-5 cells which were significantly lower than observed IC50 for AGO1522, 121.93±3.66 microM (p=0.001). Significant increase expression of 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.

Keywords: Hybrid benzoxazole-coumarin, head and Neck cancer, HN-5 cell line, apoptosis, necroptosis.

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