Exploring the anticancer potential of Hewittia malabarica through phytochemical analysis and molecular docking study

Natural resources provide valuable medicinal components that are highly sought after as alternatives to synthetic drugs for treating serious diseases like cancer. Hewittia malabarica, a creeper native to India, is recognized for its exceptional medicinal properties. In this study, the anticancer property of different solvent extracts and composition of active extract from H. malabarica were examined. Of the extracts prepared using petroleum ether, chloroform, ethyl acetate, acetone, methanol and water, the chloroform extract showed the highest cytotoxicity with an IC50 value of 31.97 +/- 3.07 mu g/mL towards HT29 cell line followed by petroleum ether extract with an IC50 value of 76.58 +/- 4.74 mu g/mL. These extracts were comparatively non-toxic to the normal human keratinocyte cell line, HaCaT, indicating its selective toxicity to cancerous cells. The cytomorphological changes associated with the chloroform extract and AO/EB dual staining indicated apoptotic cell death. An analysis of ADME properties of compounds obtained in GC-MS analysis of the chloroform extract showed that compounds such as Cyclododecanol, Sulfurous acid hexyl octyl ester, 2,4-Ditert-Butylphenol and 1,2-benzenedicarboxylic acid had favourable physicochemical and drug-likeness characteristics. When these compounds were docked on to Bax, Caspase-3 Caspase-9 and Cox-2, the proteins integral to the mitochondrial apoptotic pathway, using PyRX software, the docking score was in the range from - 4 to -6.9 kcal/mol. Particularly, 2,4-Ditert-Butylphenol showed the highest binding scores towards the selected targets. These results indicate that the mechanism of cytotoxicity observed may be mediated through induction of apoptosis in cancer cell lines. The identification of the active molecule/s in the chloroform extract will serve as drug candidate for colorectal carcinoma. Non-toxicity of the components in the extract towards normal cell line will make it selective sparing normal cells.