Abstract
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.
Highlights
New anti- cancer drugs and techniques are constantly being researched and developed in order to identify selective drugs with less adverse reactions that will mainly kill cancer cells while having fewer side effects [1]
This paper adds scientific basis to ethno pharmacological information on the health benefits of A. graveolens and suggests that it contains a selective anti-cancer compound(s) that could be developed in the future into an anti-cancer drug
We showed that A. graveolens active fractions activate cancer cell death by one or more apoptotic mechanisms, suggesting that it can be an efficient anti-cancer material as it has the potential to attack cancer cells via more than one mechanism
Summary
New anti- cancer drugs and techniques are constantly being researched and developed in order to identify selective drugs with less adverse reactions that will mainly kill cancer cells while having fewer side effects [1]. Analysis of natural products as a source of new drugs indicates that over 67% of the effective anti-cancer drugs may be traced to natural origin [2]. Asteriscus graveolens (A. graveolens) is an endemic Middle Eastern medicinal plant, located in extreme desert environments and its essential oil major component were identified as cis-chrysanthenyl acetate, myrtenyl acetate and kessane [3]. The essential oils of the aerial parts of A. graveolens contain monoterpens and sesquiterpenes including oxygenated sesquiterpenes (6-oxocyclonerolidol and 6-hydroxycyclonerolidol) as the major compIontn. The essential oils of the aerial parts of A. graveolens contain monoterpens and sesquiterpenes including oxygenated sesquiterpenes (6-oxocyclonerolidol and 6-hydroxycyclonerolidol) as the major compIontn. eJ.nMtosl.[S4c]i..2S01e8s,q1u9,ixteFrOpRePnEeERlaRcEtVoInEeWs are often used in traditional medicine against inflamm2aotfio14n and cance6r-;hfyodr reoxxaymcypclleonaerrtoelmidiosli)nians, tthheapmsiagjoarrgcionmapnodnpenatrsth[4e]n.oSleidsqeuairteeripnencleinlaiccatol ntreisalasraesotfhteeny aurseedseilnective towartrdadtuitmionoarlamneddcicaineceargsatienmst icneflllasm[5m,6a]ti.oAn.agnrdavceaonlecners; efxotrreaxcatmexphleibairtteamntisiminiinc,rothbaiaplsiagcatrigviintyan[7d] and anti-fpuanrgthaelnaocltiidveitayre[8i]n, hcloinwiceavletr,iathlsearse tahreeynaorepsueblelicsthiveedtorewpaorrdtstuomnoAr .agnrdavceaonlceners setxetmraccetsllsas[5p,6o].ssAe.ssing anti-cgarnavceeorlenascteixvtirtayc.t eAxh. igbritavaenotilmeniscrpoblaianltasctciovnityta[i7n] aanmdoanngti-ofutnhgearl macetitvaibtyo[l8it]e, sh,owseesvqeur,itehrepreenaree lnaoctone asteripsucublnisohleidderiespoomrtserosn(AAS. )g;rnavaetoulernaslleyxotrcaccutsrraisngpoAsssetsesriinsgcuannotil-icdaencAerinacdtiuvciteys. aAp.ogpratovesoilsenins ptulamntosr cell lines c[9o]n.tain among other metabolites, sesquiterpene lactone asteriscunolide isomers (AS); naturally
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