Eurycomalactone

Eurycomalactone is a natural product isolated from Eurycoma longifolia Jack., acts as a potent NF-κB inhibitor (IC50 of 0.5 μM) . Eurycomalactone inhibits protein synthesis, depletes cyclin D1, but does not affect TNFα-induced degradation of IκBα or the phosphorylation of IKKα/β and IκBα.Eurycomalactone (ECL), an active quassinoid isolated from Eurycoma longifolia Jack, has been demonstrated to possess anticancer activity. ECL exhibited selective cytotoxicity against the NSCLC cells A549 and COR-L23 compared to the normal lung fibroblast. Clonogenic survival results indicated that ECL treatment prior to irradiation synergistically decreased the A549 and COR-L23 colony number. ECL treatment reduced the expression of cyclin B1 and CDK1/2 leading to induce cell cycle arrest at the radiosensitive G /M phase. Moreover, ECL markedly delayed the repair of radiation-induced DNA double-strand breaks (DSBs) . In A549 cells, pretreatment with ECL not only delayed the resolving of radiation-induced γ-H2AX foci but also blocked the formation of 53BP1 foci at the DSB sites. In addition, ECL pretreatment attenuated the expression of DNA repair proteins Ku-80 and KDM4D in both NSCLC cells. Consequently, these effects led to an increase in apoptosis in irradiated cells. Thus, ECL radiosensitized the NSCLC cells to X-ray via G /M arrest induction and delayed the repair of X-ray-induced DSBs. It has a great potential for ECL as an alternative safer radiosensitizer for increasing the RT efficiency against NSCLC.