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

Abstract

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.

Keywords: 7,12-dimethylbenz[a]anthracene (DMBA); X-linked inhibitor of apoptosis protein (XIAP); baculovirus IAP repeat (BIR); breast cancer; liquid chromatography/mass spectrometry.