Bismuth oxide nanoparticles inhibit HCT116 colorectal cancer cells by inducing apoptosis, cell cycle arrest and ROS production

Abstract

Nanoparticles (NPs) have recently gained traction for anticancer use. Colorectal cancer (CRC) is one of the most common cancer types in the world, but only a few studies have previously reported the anticancer action of Bi₂O₃ NPs towards CRC, and the underlying mechanisms are not well understood. In this study, 1 mg/ml Bi₂O₃ NPs showed 60 % and 8 % inhibition in HCT116 and HT-29 cells, respectively. In the HCT116 spheroid, Bi₂O₃ NPs showed reduced inhibition of 27 % at 1 mg/ml due to the more stringent tissue architecture. Both CRC cells showed successful internalization of Bi₂O₃ NPs through flow cytometry and ICP-MS. The NPs mainly killed HCT116 cells by inducing late-stage apoptosis (∼17 %). In addition, Bi₂O₃ NPs also induced S and G2/M cell cycle arrest (∼4 % and ∼10 %) by targeting CDK2 protein in HCT116 cells. In HT-29 cells, Bi₂O₃ NPs did not trigger apoptosis but induced ∼22 % G2/M cell cycle arrest. Bi₂O₃ NPs also induced ROS production, and potently inhibited the cell migration. 300 μg/ml Bi₂O₃ NPs also exhibited anti-angiogenic action in the angiogenesis assay. In conclusion, the present study highlights the potential anticancer effect of Bi₂O₃ NPs towards CRC, and further investigation is warranted to improve the biocompatibility, targeted selectivity, and tumor-penetrating capacity.