Combination of fenretinide and ABT-263 induces apoptosis through NOXA for head and neck squamous cell carcinoma treatment

Autor:	Hisashi Harada, Sung W. Kim, Erin L. Britt, Sarina Raman, Kendall Leek, Casey H. Sheehy
Rok vydání:	2019
Předmět:	0301 basic medicine Adenoviruses Fenretinide Cancer Treatment Apoptosis Pathology and Laboratory Medicine Ectopic Gene Expression chemistry.chemical_compound 0302 clinical medicine hemic and lymphatic diseases Medicine and Health Sciences Retinoid Staining Sulfonamides Multidisciplinary Aniline Compounds Cell Death Squamous Cell Carcinomas Cell Staining Crystal Violet Staining Head and Neck Tumors 3. Good health Precipitation Techniques Oncology Cell Processes Medical Microbiology 030220 oncology & carcinogenesis Viral Pathogens NADPH Oxidase 2 Viruses Medicine Pathogens medicine.drug Research Article Programmed cell death medicine.drug_class Science bcl-X Protein Antineoplastic Agents Research and Analysis Methods Carcinomas Microbiology 03 medical and health sciences Head and Neck Squamous Cell Carcinoma Cell Line Tumor medicine Humans Immunoprecipitation Microbial Pathogens Cisplatin business.industry Squamous Cell Carcinoma of Head and Neck Endoplasmic reticulum Organisms Biology and Life Sciences Cancers and Neoplasms Cell Biology medicine.disease Head and neck squamous-cell carcinoma 030104 developmental biology chemistry Head and Neck Cancers Cell culture Specimen Preparation and Treatment Cancer research business DNA viruses
Zdroj:	PLoS ONE PLoS ONE, Vol 14, Iss 7, p e0219398 (2019)
ISSN:	1932-6203
Popis:	The overall survival for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) remains low, with little progress made over decades. Cisplatin, most frequently used for HNSCC treatment, activates mitochondria-dependent apoptosis through the BCL-2 family proteins. We have previously demonstrated that the pro-apoptotic BH3-only protein, NOXA plays a critical role in this process. NOXA binds and inactivates anti-apoptotic MCL-1, while the BCL-2 inhibitor ABT-263 is capable of inactivating anti-apoptotic BCL-2 and BCL-XL. We hypothesized that combination of NOXA and ABT-263 treatment increases cell death by simultaneously inhibiting anti-apoptotic BCL-2 family proteins in HNSCC cells. Here, we demonstrated that combination of ectopic NOXA expression and ABT-263 enhanced apoptosis in p53-inactive, p53 wild-type, and human papillomavirus (HPV)-positive HNSCC cell lines. Furthermore, a retinoid derivative and an endoplasmic reticulum stress inducer, fenretinide, induced NOXA, and combination of fenretinide and ABT-263 strongly induced apoptosis in HNSCC cells regardless of the HPV or p53 statuses. We also found that MCL-1 and BCL-XL are the primary targets of apoptosis induced by the combinations. These results will develop novel and alternative therapeutic strategies to directly modify the cell death machinery in HNSCC.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::61c07994654a1f46390e1f9dc524c096 https://pubmed.ncbi.nlm.nih.gov/31276572 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.