Antitumor and apoptotic activities of the chemical constituents from the ethyl acetate extract of Artemisia indica.

Cancer is one of the most eminent diseases of modern times and numerous natural products derived from medicinal plants have been identified as potential sources of antitumor drugs. A successful anticancer drug must target or inhibit tumor cells whilst causing minimal damage to healthy cells. The present study aimed to investigate the antitumor efficacy of ethyl acetate extract, and other isolated compounds from Artemisia indica, on MCF­7, BHY, Miapaca­2, Colo­205 and A­549 cell lines. The apoptotic activity of the compounds was studied using flow cytometry. The different cancer cell lines were treated with the ethyl acetate extract and varying concentrations of compounds (denoted a­g) isolated from the A. indica. The cytotoxicity was evaluated by MTT assay and the apoptotic properties of the compounds and the extract were assessed using flow cytometry. In MCF­7 cells, the effect on mitochondrial membrane potential loss (ΛΨm) induced by compounds b and d was also studied. Bioassay­guided fractionation of the ethyl acetate extract from the shoot and root parts of A. indica led to the identification of the compounds a­g as: 5­hydroxy­3,7,4'­trimethoxyflavone; ludartin; maackiain; lupeol; cis­matricaria ester; trans­matricaria ester; and 6­methoxy­7,8­methylenedioxy coumarin, respectively. All the compounds exhibited mild to potent inhibition of cell proliferation in all the cell lines, with the half maximal inhibitory concentration values ranging from 25.18­88.12 µM. Ludartin and lupeol were observed to have the most potent inhibitory effects. Based on the initially identified antiproliferative effects, these two compounds were evaluated for their effects on cell cycle phase distribution, DNA damage and their effects on mitochondrial membrane potential loss (ΛΨm). The two compounds induced DNA damage and mitochondrial membrane potential loss in MCF­7 cells. The results of the current study suggest that lupeol and ludartin, isolated from A. indica, produce anticancer effects by inducing DNA damage and a reduction of mitochondrial membrane potential, and may be used as potent anticancer agents, subsequent to further study.