PO-076 HMNQ induces apoptosis and autophagy dependent on reactive oxygen species through activation of JNK signalling pathway

Abstract

Introduction8-hydroxy-2-methoxy-1,4-naphthoquinone (HMNQ), a natural compound isolated from bark of Juglans sinensis Dode, has been previously reported to possess cytotoxic activity toward various human cancer cells. However, the molecular mechanism of its anticancer effect remains unknown.Material and methodsIn this study, the anticancer activity and molecular mechanism of HMNQ were investigated using cell viability/colony formation assay and wound healing assay. In addition, apoptosis analysis and measerement of mitochondria membrane potential were performed.Results and discussionsOur results showed that HMNQ reduced cell viability, decreased colony formation, and inhibited cell migration in breast, lung, and colon cancer cells. HMNQ effectively induced apoptosis by upregulating the expression of pro-apoptotic protein Bax, cleaved PARP, and downregulating the expression of anti-apoptotic protein Bcl-2 in A549 and MCF7 cells. In addition, HMNQ also induced reactive oxygen species (ROS) production through the decreased mitochondrial-membrane potential and this effect was attenuated by ROS scavengers, N-acetylcysteine (NAC) and l-glutathione (GSH). Furthermore, HMNQ increased the expression of JNK phosphorylation and JNK inhibitor SP600125 suppressed HMNQ-induced decrease in cell viability.ConclusionTaken together, our findings suggest that HMNQ exhibits anti-proliferative activity through induction of ROS-mediated apoptosis in human cancer cells, indicating that HMNQ as a potential anticancer agent.