Gallic acid‐loaded chitosan nanoparticles enhance the DNA damage and apoptotic features through inhibiting flap endonuclease‐1 in triple‐negative breast cancer cells

Abstract

AbstractThis study investigated the fabrication of gallic acid‐loaded chitosan nanoparticles (Gal‐Chi‐NPs) that enhanced the DNA damage and apoptotic features by inhibiting FEN‐1 expressions in MDA‐MB 231 cells. Gal‐Chi‐NPs were fabricated by the ionic gelation method, and it was characterized by several studies such as dynamic light spectroscopy, Fourier‐transforms infrared spectroscopy, x‐ray diffraction, scanning electron microscopy, energy‐dispersive x‐ray, atomic force microscopy, and thermogravimetric analysis. We have obtained that Gal‐Chi‐NPs displayed 182.2 nm with crystal, smooth surface, and heat stability in nature. Gal‐Chi‐NPs induce significant toxicity in MDA‐MB‐231 cells that compared with normal NIH‐3T3 cells. A significant reactive oxygen species (ROS) overproduction was observed in Gal‐Chi‐NPs treated MDA‐MB‐231. Flap endonuclease‐1 (FEN‐1) is a crucial protein involved in long patch base excision repair that is involved in repairing the chemotherapeutic mediated DNA‐damaged base. Therefore, inhibition of FEN‐1 protein expression is a crucial target for enhancing chemotherapeutical efficacy. In this study, we have obtained that Gal‐Chi‐NPs treatment enhanced the DNA damage by observing increased p‐H2AX, PARP1; and suppressed the expression of FEN‐1 in MDA‐MB‐231 cells. Moreover, Gal‐Chi‐NPs inhibited the expression of tumor proliferating markers p‐PI3K, AKT, cyclin‐D1, PCNA, and BCL‐2; induced proapoptotic proteins (Bax and caspase‐3) in MDA‐MB 231 cells. Thus, Gal‐Chi‐NPs induce DNA damage and apoptotic features and inhibit tumor proliferation by suppressing FEN‐1 expression in triple‐negative breast cancer cells.