Doxorubicin induced apoptosis was potentiated by neferine in human lung adenocarcima, A549 cells

Abstract

Doxorubicin (DOX) is the best anticancer agent that has ever been used, but acquired tumor resistance and dose limiting toxicity are major road blocks. Concomitant use of natural compounds is a promising strategy to overcome this problem. Neferine, a proven anticancer agent is found in green embryos of lotus seed. The study demonstrates that neferine acts as an effective enhancer of DOX-induced cell death in A549 cells through ROS mediated apoptosis with MAPK activation and inhibition of NF-κB nuclear translocation. Cotreatment of cells with neferine significantly enhanced intracellular DOX-accumulation. Neferine and DOX in combination also triggered oxidative stress through intracellular Ca(2+) accumulation and dissipation of mitochondrial membrane potential in addition to significant loss of cellular antioxidant pool. The MAPK inhibitor effectively decreased the cell-death induced by neferine and DOX. Pretreatment of cells with glutathione reversed the apoptosis induced by combined regimen and recovered the Bcl2/Bax ratio. Moreover, neferine treatment significantly increased the cell viability of DOX-treated cardiomyocytes indicating a possible protective role of neferine towards DOX-induced cardiotoxicity. Taken together, our results suggest that a strategy of using neferine and DOX in combination could be helpful to increase the efficacy of DOX and to achieve anticancer synergism by curbing the toxicity.

Keywords: Apoptosis; Doxorubicin; MAPK; NF-κB; Neferine; ROS.