Crinum jagus: antiproliferative studies of extracts on HepG2 cell line and in silico assessment of phytoconstituents as potential inhibitors of p53–mortalin interaction

Abstract Background Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide and has a poor prognosis in black Africans. Traditional herbal practitioners in southwestern Nigeria use Crinum jagus (J. Thompson) Dandy for cancer treatment. This study screens methanol and ethyl acetate extracts of C. jagus leaves for activity against hepatocellular carcinoma (HepG2) cell line using the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay. The antiproliferative properties of the extracts were assessed by comparing their IC50 values with that of the standard drug, cisplatin. The GC–MS technique was used to identify the phytoconstituents in the extracts. The drug-likeness of each identified phytoconstituents in the extracts was determined by following Lipinski’s rule of five. In addition, phytoconstituents having drug-like properties were screened as potential inhibitors of the p53–mortalin interaction by docking them against the mortalin residues 3N8E and 4KBO using Swissdock. Results For the antiproliferative study, the IC50 values obtained for cisplatin, methanol, and ethyl acetate extracts of leaves were 5 µg/mL, 5 µg/mL, and 70 µg/mL, respectively, indicating that the methanol extract and cisplatin possess comparable antiproliferative properties. Hexadecanoic acid, hexadecanoic acid methyl ester, tangeretin, galanthamine, and crinamine, which were part of the constituents identified in the leaves, possess drug-like properties and are known to show cytotoxic properties against several cancer cell lines. On docking with mortalin residue 3N8E, hexadecanoic acid and hexadecanoic acid methyl ester had comparable binding energy (− 8.21 kcal mol−1) with withaferin A and withanone (8.29 kcal mol−1 and 8.14 kcal mol−1). Hexadecanoic acid, hexadecanoic acid methyl ester, and galanthamine had binding energy of − 7.66, − 7.45, and − 7.47 kcal mol−1, respectively, with mortalin residue, 4KBO, comparable to values of − 7.68 and − 7.59 kcal mol−1 obtained for withaferin A and withanone, respectively. Conclusion The methanol extract of C. jagus leaves demonstrated remarkable antiproliferative activities against HepG2, justifying its use in traditional medicine for cancer treatment. The ethyl acetate and methanol extracts contain drug-like compounds with known cytotoxic properties against several cancer cell lines. Some of these compounds (hexadecanoic acid, hexadecanoic acid methyl ester, tangeretin, and galanthamine) are inhibitors of the p53–mortalin interaction. Graphical Abstract