Unveiling the polypharmacology mechanistic role of steroidal scaffolds from Spondia mombin L. (Anacardiaceae) on EGFR, VEGF, and mTOR: validation of usage in colorectal cancer management in Southwestern Nigeria

Abstract

Natural products in conjunction with computer-aided drug design have made a significant impact in the development of novel therapeutics in a fast manner in modern-day drug discovery. Spondia mombin has been reported among locals to be effective in the management of colon cancer. Hence, this study was conducted to experimentally justify the anti-tumor properties of Spondia mombin amongst locals using the combination of benchtop cytotoxicity [Ranicep ranninus (RR) and Saccharomyces cerevisiae (SC)] and human HCT 116 colon cancer cell line (Sulfordiamine B assay) as well as computational chemistry models. The crude extract (CSM) and an aqueous fraction of S. mombin (ASM) at 20–100 µg/mL showed 80–100% mortality of RR, while 7.81–250 µg/mL of CSM and ASM also exhibited 70–95% cytotoxic effect of SC. A 2.02% increase in cytotoxic effect on colorectal cancer cell line (human HCT 116) was observed in ASM (IC₅₀—22.23 ± 2.56 µg/mL) relative to 21.78 ± 2.98 µg/mL observed in CSM. Gramisterol, campesterol, chalinasterol, obtusifoliol, beta-sitosterol, stigmasterol, and betulin isolated from CSM (from literature) were shown to possess steroidal scaffold, they were observed to show promising anti-colon cancer properties via antagonistic influence on epidermal growth factor receptor, vascular endothelial growth factor receptor, and mammalian target of rapamycin colon receptors through van der Waal, alkyl, carbon-hydrogen, conventional hydrogen, and pi-alkyl interactions with the amino acid residues in the binding sites of the receptors. Findings from this research experimentally justify the ethnopharmacological claim of S. mombin in the treatment of colon cancer via antagonist polypharmacological action of the steroidal compounds on different receptors implicated in colon cancer carcinogenesis.