Metibemu Damilohun Samuel, Akinloye Oluseyi Adeboye, Akamo Adio Jamiu, Okoye Jude Ogechukwu, Ojo David Ajiboye, Morifi Eric, Omotuyi Idowu Olaposi
Department of Biochemistry, Adekunle Ajasin University, Akungba-Akoko, Nigeria.
Department of Biochemistry, Federal University of Agriculture, Abeokuta, Nigeria.
J Food Biochem. 2020 Dec;44(12):e13523. doi: 10.1111/jfbc.13523. Epub 2020 Oct 20.
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.
乳腺癌是女性中最常见的癌症。在癌症中持续过度表达的X连锁凋亡抑制蛋白（XIAP）是癌症治疗中一个有前景的治疗靶点。本研究通过XIAP拮抗作用，研究了腰果树（Spondias mombim）类胡萝卜素提取物对Wistar大鼠二甲基苯并蒽（DMBA）诱导的乳腺癌的抗癌作用机制。对从腰果树叶片中分离出的类胡萝卜素进行液相色谱/质谱联用（LC/MS）和电喷雾电离（ESI）分析以进行表征。将表征后的类胡萝卜素提取物与XIAP的BIR2结构域和XIAP的BIR3结构域进行对接。还通过qRT-PCR检测XIAP、COX-2、TNF、BCl-2 mRNA的表达以及过氧化氢酶、脂质过氧化、乳酸脱氢酶（LDH）、碱性磷酸酶（ALP）和谷丙转氨酶（ALT）的生化参数，研究了腰果树类胡萝卜素提取物对Wistar大鼠DMBA诱导的乳腺癌的抗癌作用。这些结果表明，类胡萝卜素提取物通过拮抗XIAP、促凋亡和抗炎特性发挥抗癌作用。实际应用：本研究表明，从腰果树叶片中分离出的类胡萝卜素（虾青素、β-胡萝卜素-15,15'-环氧化物和7,7',8,8'-四氢-β,β-胡萝卜素）具有促凋亡作用，这进一步证实了类胡萝卜素的化学预防能力。本研究验证了XIAP是癌症治疗中的一个可成药靶点，因此应针对它筛选更多植物化学物质，以寻找可能的植物源先导化合物。癌细胞经常利用XIAP产生抗凋亡和耐药倾向，因此，β-胡萝卜素-15,15'-环氧化物和7,7',8,8'-四氢-β,β-胡萝卜素（XIAP拮抗剂）是有前景的候选药物，能够抵抗耐药和易发生凋亡的癌细胞。有必要合成β-胡萝卜素-15,15'-环氧化物和7,7',8,8'-四氢-β进行临床研究的进一步调查。
