Chitosan-gold nanoparticles trigger apoptosis in human breast cancer cells in vitro

Abstract

Despite profound advancement in the field of cancer treatment, the disease is still one of the deadliest in the world. In this aspect, nanotechnology is emerging as a highly promising area to be focussed upon. In this study, we investigated the cytotoxic effect of synthesized chitosan-functionalized gold nanoparticles (G1) having a diameter of 15–20 nm on hormone-responsive MCF7 and hormone therapy-resistant MDA-MB-231 breast cancer cell lines. We found significant mortality of these two cancer cell types with the IC50 as low as ~ 11 ppb just after 48 h of treatment without exhibiting any cytotoxic effect on normal human peripheral blood lymphocytes. In both cancer cell lines, G1 induced severe cytomorphological alterations and reactive oxygen species overload with subsequent activation and nuclear translocation of master stress-regulator Nrf2 as an antioxidant response. Consequently, nuclear fragmentation and subsequent apoptotic cell death were evident that progressed primarily through activation of the Bax–Caspase9–Caspase3–PARP1 axis being concomitant with p53–p21 mediated cell cycle arrest. Moreover, disturbed homeostasis of cellular elements like copper, chlorine, potassium, sulfur, selenium and calcium further strengthened our findings. Therefore, G1 can be concluded as highly effective against two major types of breast cancer cells without any significant toxic effect in normal cells which might popularize it as a potent candidate for breast cancer therapeutics warranting further research.