Molecular Mode of Action of Asteriscus graveolens as an Anticancer Agent.

Asteriscus graveolens (A. graveolens) plants contain among other metabolites, sesquiterpene lactone asteriscunolide isomers (AS). The crude extract and its fractions affected the viability of mouse BS-24-1 lymphoma cells (BS-24-1 cells) with an IC50 of 3 μg/mL. The fraction was cytotoxic to cancer cells but not to non-cancerous cells (human induced pluripotent stem cells); its activity was accompanied by a concentration- and time-dependent appearance of apoptosis as determined by DNA fragmentation and caspase-3 activity. High levels of Reactive Oxygen Species (ROS) were rapidly observed (less than 1 min) after addition of the fraction followed by an increase in caspase-3 activity three hours later. Comparison of RNA-seq transcriptome profiles from pre-and post-treatment of BS-24-1 cells with crude extract of A. graveolens yielded a list of 2293 genes whose expression was significantly affected. This gene set included genes encoding proteins involved in cell cycle arrest, protection against ROS, and activation of the tumor suppressor P53 pathway, supporting the biochemical findings on ROS species-dependent apoptosis induced by A. graveolens fraction. Interestingly, several of the pathways and genes affected by A. graveolens extract are expressed following treatment of human cancer cells with chemotherapy drugs. We suggest, that A. graveolens extracts maybe further developed into selective chemotherapy.