Anticancer potential of two Helichrysum italicum extracts obtained by supercritical CO2 extraction

Introduction The plant species belonging to the large genus Helichrysum are a valuable source of bioactive compounds. The aim of this study was to investigate the anticancer properties of the two Helichrysum italicum extracts obtained from plant material by supercritical CO2 extraction. Material and Methods The cytotoxicity of the extracts was examined against six human cancer cell lines: cervical adenocarcinoma HeLa, lung carcinoma A549, prostate adenocarcinoma PC-3, breast adenocarcinoma MCF-7, melanoma A375, and chronic myelogenous leukemia K562, as well as against two human normal cell lines: lung fibroblasts MRC-5 and keratinocytes HaCaT. Cell cycle analysis was performed by flow cytometry. Gene and microRNA expression levels were measured by RT-qPCR. Results and Discussions The H. italicum extracts exerted concentration-dependent and selective cytotoxic effects on cancer cells. HeLa, A375, and K562 cells were the most sensitive to the cytotoxic activity of both extracts. The extracts showed lower intensities of cytotoxic activity against normal HaCaT cells when compared with intensities of activity against K562, A375, and HeLa cells. An increases in the percentages of cells within subG1 and S phases of the cell cycle were observed in HeLa cells incubated for 24 h with IC50 and 2IC50 concentrations of the extracts in comparison with control cells. A similar effect on the cell cycle phase distribution was seen in A375 cells after 24 h incubation. The G2/M phase arrest was also detected in A375 cells exposed to IC50 concentrations of the extracts. Both extracts induced apoptosis in HeLa cells through the activation of effector caspase-3. The extracts triggered apoptosis through the intrinsic pathway mediated by caspase-9 and the extrinsic pathway mediated by caspase-8. Each of the extracts decreased expression levels of MMP2 in HeLa cells, slightly increased levels of MMP9, and increased levels of VEGFA. Up-regulations of genes involved in cancer invasion and pro