Naringin inhibits growth and induces apoptosis by a mechanism dependent on reduced activation of NF-κB/COX-2-caspase-1 pathway in HeLa cervical cancer cells

Naringin (NRG), a bioflavonoid found in citrus fruit extracts, has been pharmacologically evaluated as a potential anticancer agent. This study confirmed a novel mechanism of the anticancer effects of NRG in the human cervical cancer HeLa cell line (HeLa cells). Exposure of HeLa cells to NRG resulted in growth inhibition, as evidenced by a decrease in cell viability. In addition, NRG treatment induced apoptosis, as indicated by the increased apoptotic percentage and the cleaved caspase-3 expression. Importantly, exposure of the cells to NRG attenuated the expression levels of phosphorylated (p) nuclear factor κB (NF-κB) p65 subunit, cyclooxygenase-2 (COX-2) and cysteinyl aspartate proteinase-1 (caspase-1). Treatment with PDTC (an inhibitor of NF-κB) or NS-398 (an inhibitor of COX-2) or SC-3069 (an inhibitor of caspase-1) markedly induced growth inhibition and apoptosis. Treatment with PDTC or NS-398 also reduced caspase-1 expression. Interestingly, PDTC treatment blocked the expression of COX-2 and NS-398 reduced the p-NF-κB p65 expression. Taken together, this study provides novel evidence that NRG induces growth inhibition and apoptosis by inhibiting the NF-κB/COX-2-caspase-1 pathway and that a positive interaction between NF-κB and COX-2 pathway contributes to the growth and antiapoptotic effect in HeLa cells.