Piperlongumine Induces Gastric Cancer Cells Apoptosis And G2/M Cell Cycle Arrest Both In Vitro And In Vivo

Background and Objectives:Recently,several studies have shown that piperlongumine(PL)can selectively kill cancer cells by targeting reactive oxygen species(ROS).However,the potential therapeutic effects and detailed mechanism of piperlongumine in gastric cancer are still not clear.Our study aim to invistigate the effect of piprelongumine on gastric cancer in vitro and in vivo.METHOD:Gastric cancer cell lines AGS and HGC27 were treated with different doses of PL,caspase inhibitor,antioxidant,and their combinations,respectively.Cell viability was assessed by CCK-8 assay;cell cycle,apoptosis and intracellular ROS level were measured by flow cytometry;Small interfering RNA was used to knockdown the expression of STAT3 and GADD45a and Western blotting was employed to determine the expression of the associated protein.Xenograft experiment to examine the antitumor effect of piperlongumine in mice.RESULT:Piperlongumine significantly suppressed gastric cancer both in vitro and in vivo.Piperlongumine obviously increased ROS generation in gastric cancer cells.Antioxidant GSH and NAC can abrogate piperlongumine-induced gastric cancer cell death and proliferation inhibition.GADD45? was induced in piperlongumine-treated cancer cells and led to G2/M phase arrest,whereas genetic depletion of GADD45a by small interfering RNAs(siRNAs)could partly reverse piperlongumine-induced cell cycle arrest in gastric cancer cells.Interestingly,we also found that piperlongumine treatment decreased the expression of telomerase reverse transcriptase(TERT)gene,which plays an essential role in cancer initiation and progression.Piperlongumine exhibited apparent antitumour effect in vivo.CONCLUSION:Our findings thus revealed a potential antitumor effect of piperlongumine on gastric cancer cells and may have therapeutic implications.