Mukonal exerts anticancer effects on the human breast cancer cells by inducing autophagy and apoptosis and inhibits the tumor growth in vivo

Abstract

AbstractMukonal is an active member of carbazole alkaloids isolated from Murraya koenigii. It has been shown to possess remarkable biological and pharmacological activities including anticancer activity. Therefore, the aim of current investigation was to explore anti-breast cancer activity of mukonal and to explore the underlying mechanism. Results indicate that mukonal has potential to induce antiproliferative effects against MDA-MB-231 and SK-BR-3 cells with an IC50 of 7.5 µM. No significant toxicity of mukonal was observed in case of normal breast cells. The antiproliferative effects of mukonal were found to proceed via apoptosis, which was further supported by increased cleavage of PARP and caspase-3 and reduced expression of Bcl-2. Mukonal induced autophagic cells death in breast cancer cells as was evidenced by formation of autophagosomes and enhanced expressions of Beclin-1, LC3B-I and LC3B-II proteins. In vivo examination of anti-breast cancer property of mukonal indicated that it could potentially reduce tumor weight and volume in xenografted mice models. In conclusion, mukonal has a remarkable potential of inhibiting breast cancer via induction of apoptosis and autophagy. Mukonal also inhibited xenografted tumors models in a dose-dependent manner. Therefore, mukonal may prove lead molecule in breast cancer drug discovery and treatment provided further investigations are recommended.