Silver nanoparticle-induced alteration of mitochondrial and ER homeostasis affects human breast cancer cell fate. (2022)

• Record Type: Journal Article
• Authors: Dey, Smita; Fageria, Leena; Sharma, Ankita; Mukherjee, Sudeshna; Pande, Surojit; Chowdhury, Rajdeep; Chowdhury, Shibasish
• Is Part Of: Toxicology reports. Volume 9(2022)
• Page Start: 1977
• Page End: 1984
• Publication Date: 2022
• Subjects: Silver nanoparticles -- Mitochondria -- Endoplasmic reticulum; Toxicology -- Periodicals; Clinical toxicology -- Periodicals; Drug-Related Side Effects and Adverse Reactions; Hazardous Substances; Poisoning; Toxicology; Electronic journals; Periodicals; Periodicals; 571.9505
• DOI: 10.1016/j.toxrep.2022.10.017
• Languages: English
• ISSNs: 2214-7500

Abstract

Abstract: Breast cancer is one of the most frequent forms of cancer. Although different treatment modalities are available, none has proved to be a game-changer. In this context, nanomedicine is one of the hot research areas, with different nano-formulations being explored as a therapeutic strategy against breast cancer. Herein, silver nanoparticles (AgNPs) have shown prospects with their anti-tumor properties and are currently being explored aggressively; however, the underlying molecular mechanisms of AgNP action remain to be unearthed. As part of this study, human breast cancer cells- MCF7 were exposed to AgNPs (∼9 nm), and the effect of the same was explored on mitochondrial and endoplasmic reticulum (ER) dynamicity. We observed that the AgNPs co-localize with mitochondria and cause mitochondrial membrane depolarization, ROS generation, and destabilized mitochondrial homeostasis. Also, the NPs were found to enhance ER stress. We further found that increased ER stress is linked to the disruption of mitochondrial dynamics. Overall, our study shows that the AgNPs can effectively cause apoptosis of MCF-7 cells by regulating the mitochondrial-ER dynamicity. The results provide an insight into the mechanisms via which AgNPs act and can be used in developing a potential chemotherapeutic agent. Graphical Abstract: ga1 Highlights: AgNPs enter mitochondria, cause membrane depolarization and mitochondrial ROS generation. AgNPs cause mitochondrial fragmentation and fission. AgNPs induces ER stress and disrupt ER morphology. Increased ER stress leads to more mitochondrial damage and cell death.