Heterocyclic organic compounds extracted from Artemisia judaica (L.) induced caspase-dependent mitochondrial pathway in different breast and liver cancer cell lines: In silico and in vitro studies

Abstract

Oestrogen-dependent cancers, such as breast and liver cancer, depend on oestrogen to develop and grow rapidly. This study evaluated the anticancer activity of extracted heterocyclic compounds from Artemisia judaica (L.) as alternative drug candidates against different oestrogen-sensitive cancer cells. Fresh A. judaica leaves were macerated in 80% ethanol and evaporated using an yellow browncrude extract. Tri-spectroscopy and molecular analytical techniques were used to identify the extracted compounds' bioactive constituents and binding stability. Different normal HSF, and cancer cell lines MCF-7, T47D, MDA-MB-231, and HePG2 were treated with various concentrations of doxorubicin and A. judaica extract for twenty-four h and forty-eight h. The cytotoxic activity of the extracted compounds was evaluated using bio-viability assays. The extracted heterocyclic compounds (benzamide, N-[4-(1H-1,3-benzimidazol-2-yl)-1,2,5-oxadiazol-3-yl] -4-fluoro-, 3-phenyl-6-(4-nitro-phenyl) -4H-(1,2,3) triazole (1,5-d) (1,3,4) oxadiazin-4-one, 2-benzofurancarboxylic acid, 7-methoxy-, (3,4,4-trimethyl-1,2-dioxetan-3-yl) methyl ester, and 2-amino-4,6-diphenyl-pyrimidine) exhibited moderate to well-qualified water solubility, well-binding affinity, and stability with caspase-3, and showed no cytotoxic effects on normal HSF cells with a value of 923.9 ± 5.33 µg/mL and a selectivity index (SI > 2). In contrast, significant inhibition in cell proliferation was observed, particularly in MDA-MB-231 cells with values of 152.7 ± 3.18 µg/mL and 55.18±2.03 µg/mL after 24 and 48 h, respectively, with increased levels of ROS, disruption of MMP that led to increased caspase-3 enzyme, and subsequent induction of cell cycle arrest and apoptosis. We found that atoms such as nitrogen in the extracted heterocyclic compounds made them excellent anticancer medications by targeting DNA and inhibiting oestrogen-sensitive cancer cell progression.