Gold nanoparticles exhibit anticancer property through induction of oxidative stress and autophagy in MCF-7 breast cancer cells

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Abstract
The low cost, and pro-apoptotic property of gold nanoparticles (AuNPs) make them an attractive candidate for the investigation in cancer therapy. Despite promising advances made in cancer research using AuNPs, the molecular mechanisms involved in AuNPs-induced cell death is still remaining largely unknown. This study was undertaken to elucidate the anticancer property of AuNPs by determining the involvement of AuNPs-induced reactive oxygen species (ROS) in the stimulation of autophagy in MCF-7 human breast cancer cells. In this experimental study MCF-7 cells were cultivated in 6-well plates in the presence or absence of AuNPs for 24 h. In addition, to confirm the pivotal role of AuNPs in ROS generation, AuNPs-treated cells were also cultured in the presence of N-acetylcysteine (NAC; as an antioxidant agent) and hydroxychloroquine (HCQ; as an inhibitor of autophagosome formation). Then, the ROS contents of the cells were determined and the effects of AuNPs in the formation of autophagosome and induction of apoptosis were investigated. Also, the relative expression levels of Bax, Bcl2, MAPK P38, JNK, Beclin-1, and LC3 mRNA were analyzed by RT-qPCR and the protein contents of LC3-I/II and Beclin-1 were measured. AuNPs-induced generation of ROS was prevented by the administration of NAC. AuNPs increased formation of autophagosomes and enhanced the expression of autophagy-related proteins such as LC3 and Beclin-1. Moreover, AuNPs triggered apoptosis, increased the ratio of Bax to Bcl-2 gene expression level, and resulted in the loss of mitochondrial membrane potential. In AuNPs-treated cells, the involvement of ROS in boosting autophagy process and increasing apoptosis was confirmed by the ROS-scavenging effects of NAC which successfully suppressed ROS level and prevented autophagy and apoptosis. Our finding suggest that AuNPs-induced ROS can promote autophagy and apoptosis via mitochondrial dysfunction and regulation of the ROS/JNK signaling pathway in MCF-7 cancer cells. Thereby highlighting the potential therapeutic value of AuNPs as anticancer agents.

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