Carotenoid isolates of Spondias mombin demonstrate anticancer effects in DMBA-induced breast cancer in Wistar rats through X-linked inhibitor of apoptosis protein (XIAP) antagonism and anti-inflammation

Autor:	Idowu Olaposi Omotuyi, Eric Morifi, Jude Ogechukwu Okoye, D.A. Ojo, Adio Jamiu Akamo, Oluseyi Adeboye Akinloye, Damilohun Samuel Metibemu
Rok vydání:	2020
Předmět:	030309 nutrition & dietetics Anacardiaceae Biophysics Anti-Inflammatory Agents DMBA X-Linked Inhibitor of Apoptosis Protein Pharmacology Inhibitor of apoptosis Lipid peroxidation 03 medical and health sciences chemistry.chemical_compound 0404 agricultural biotechnology Neoplasms medicine Animals Rats Wistar 0303 health sciences Chemistry Cancer 04 agricultural and veterinary sciences Cell Biology medicine.disease 040401 food science Carotenoids XIAP Rats Cancer cell Tumor necrosis factor alpha Antagonism Food Science
Zdroj:	Journal of food biochemistryREFERENCES. 44(12)
ISSN:	1745-4514
Popis:	Breast cancer is the most prevalent cancer in women. X-linked inhibitor of apoptosis protein (XIAP) that is constantly overexpressed in cancer is a promising therapeutic target in cancer treatments. The mechanisms of the anticancer effects of carotenoid isolates of Spondias mombim in DMBA-induced breast cancer in Wistar rats through XIAP antagonism were investigated in the present study. Carotenoids isolated from the leaves of Spondias mombim were subjected to Liquid Chromatography/Mass Spectrometry (LC/MS) and Electrospray Ionization (ESI) for characterization. The characterized carotenoid isolates were docked against XIAP BIR2 domain and XIAP BIR3 domain. The anticancer effects of the carotenoid isolates of Spondias mombim in DMBA-induced breast cancer in Wistar rats were also investigated through the expression of XIAP, COX-2, TNF, BCl-2 mRNAs by qRT-PCR and biochemical parameters of catalase, lipid peroxidation, LDH, ALP, and ALT. These show the carotenoid isolates demonstrate anticancer effects by antagonism of XIAP, proapoptotic, and anti-inflammatory properties. PRACTICAL APPLICATIONS: The present study showed that carotenoids (astaxanthin, β-carotene-15,15'-epoxide, and 7,7',8,8'-tetrahydro-β, β-carotene) isolated from the leaves of Spondias mombim are proapoptotic, it further gives credence to the chemopreventive abilities of carotenoids. This study validated XIAP as a druggable target in cancer treatment and hence more phytochemicals should be screened against it, for possible lead compounds of plant origin. Cancer cells often explore XIAP for antiapoptotic and resistance tendencies, hence, β-carotene-15,15'-epoxide and 7,7',8,8'-tetrahydro-β, β-carotene (XIAP antagonists) are promising drug candidates that can withstand resistant and prone cancer cells to apoptotic cell death. There is a need to synthesize β-carotene-15,15'-epoxide and 7,7',8,8'-tetrahydro-β for further investigation in clinical studies.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e8dc5c536ebdce7ec1eb6511c878cc0a https://pubmed.ncbi.nlm.nih.gov/33084091 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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