COX-2 and survivin reduction may play a role in berberine-induced apoptosis in human ductal breast epithelial tumor cell line

Berberine is an isoquinoline alkaloid that has several pharmacological effects such as antiinflammatory, antimicrobial, apoptosis-inducing and anticancer effects. It has been illustrated that the antiinflammatory effect is mediated by suppressing the nuclear factor-kappa B (NF-kappa B) that activates expression of some antiinflammatory and antiapoptotic proteins including cyclooxygenase-2(COX-2), inducible nitric oxide synthase (iNOS) and survivin; therefore, berberine may induce apoptosis by reducing antiinflammatory and antiapoptotic agents, which suggest the relationship between antiinflammatory and apoptosis pathways. For further illustration of the mechanism of berberine action, the human ductal breast epithelial tumor cell line (T47D cell line) was treated with different concentrations of berberine (25-100 mu M/ml). Berberine in 50 mu M/ml had the most reducing effect on cell viability and inducing of apoptosis. The level of COX-2, iNOS and survivin proteins decreased in berberine-treated cells; however, treatment of the cells with aspirin and aminoguanidine (AG), COX-2 and iNOS inhibitors, respectively, showed that despite the cell growth-reducing effect of aspirin, AG did not have a significant effect on cell viability. On the other hand, with the attention to reduction in survivin protein level in berberine-treated cells, the results suggest that the apoptotic effect of berberine may be mediated by reduction in both of the COX-2 and survivin in T47D cell line, while the iNOS does not play any effective role in berberine-induced apoptosis.