S-Allyl Cysteine-Functionalized Zinc Oxide Nanoparticles Induce p53-Mediated Apoptosis and DNA Fragmentation in Colorectal Adenocarcinoma
摘要
Functionalization of green-synthesized nanoparticles (NPs) is emerging as a strategy to develop NPs with improved biocompatibility for cancer treatment. In the present study, zinc oxide NPs (ZnONPs) were synthesized using Moringa oleifera leaf extract. Subsequently, it was functionalized with s-allyl cysteine (SAC) to obtain SAC@ZnONPs. The SAC@ZnONPs was characterized using UV–visible spectroscopy, X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), FESEM–EDAX, and dynamic light scattering (DLS). Further, the anticancer effect of SAC@ZnONPs against the human colorectal cancer cell line (HT-29) was studied. Functionalization of ZnONPs with SAC has decreased the aggregation of ZnONPs. Further, functionalization enhanced colloidal stability, as evidenced by increased hydrodynamic size and a shift toward a more negative zeta potential. SAC@ZnONPs exhibited significant, concentration-dependent cytotoxicity in HT-29 cells, while showing minimal toxicity toward HEK293 cells, resulting in a high selectivity index. The mechanism of the anticancer effect by SAC@ZnONPs includes ROS generation, MMP destabilization, DNA fragmentation, and increased mRNA levels of pro-apoptotic proteins (p53, Bax and caspase 3). Altogether, these molecular level changes have converged into apoptosis in SAC@ZnONPs-treated HT-29 cells. Further, in vivo studies are warranted to fully understand the therapeutic potential of SAC@ZnONPs against colorectal cancer.