Novel anti-cancer role of naphthazarin in human gastric cancer cells

Gastric cancer is one of the most common malignant tumors and the secondcause of cancer-related deaths worldwide. Naphthoquinones such as juglone andplumbagin are compounds used extensively to overcome resistance to chemotherapeuticagents in cancers due to their cytotoxic role. This study is the first to investigatethe anti-cancer effect of naphthazarin (Naph), one of the naphthaquinones, inhuman gastric cancer AGS cells. We showed that Naph exhibited effective preferentialcell growth inhibition via G2/M phase arrest and apoptosis, which was associatedwith reduced levels of Cdc2 and Cdc25C expression. Naph also increased cleavedcaspase-3 and Poly ADR(adenosine diphosphate ribose) Polymerase expression, γ-H2AXexpression (an indicator of DNA double strand breaks) and DNA fragmentation. Wealso found the generation of reactive oxygen species is a critical mediator inNaph-induced cell growth inhibition and apoptosis. The non-protein antioxidant,glutathione significantly abolished Naph-mediated inhibition of cell growth andapoptosis. Taken together, our findings showed that Naph not only inhibited cellgrowth, but also induced apoptosis of AGS cells, suggesting that Naph may be apotential candidate for cancer therapy against gastric cancers.