Strychnine-induced Apoptosis In Non-small Cell Lung Cancer Cell Line A549 Mechanism

Objective:Nux vomica is one of active components from Strychnos nux vomica, with significant analgesic, anti-inflammatory and platelet-aggregating inhibitory properties. Due to its cytotoxic effect, the anti-tumor effect of Nux vomica has increasingly been appreciated. In this study, we investigated the effect of Nux vomica on A549 cells proliferation, apoptosis as well as the underlying mechanisms. Methods:MTT assay was used to examine the cell viability, flow cytometric analysis and fluorescent microscope were applied to examine cell apoptosis, ELISA method was used to examine the effect of Nux vomica on PGE2 release from A549 cells and RT-PCR analysis was used to measure mRNA content, western blotting analysis was used to measure protein expression and luciferase activity was used to examine the effect of Nux vomica on cox-2 promoter activity. Results:Nux vomica was able to time-dependently and dose-dependently suppress the proliferation of A549 cells and induce cell apoptosis. To understand the mechanisms, cox-2 was identified to be an important target molecule involved in the apoptotic effect of Nux vomica, because Nux vomica dose-dependently suppressed the cox-2mRNA, protein expressions as well as PGE2 release in A549 cells. Furthermore, overexpression of cox-2 abrogated Nux vomica-induced cell apoptosis, in contrast, when A549 cells were transfected with cox-2 siRNA, the apoptotic effect of Nux vomica was dramatically enhanced. Further analysis revealed that Nux vomica was able to suppress cox-2 transcriptional activation. Conclusion:This paper described for the first time that Nux vomica was able to induce lung cancer apoptosis via downregulation of cox-2. By structural modification, chemicals with similar structure as Nux vomica are likely to be developed as effective anti-tumor agents.