Inorganic titanium dioxide nanoparticles induces cytotoxicity in colon cancer cells

Abstract

Globally, colorectal cancer (CRC) is responsible for 10% of the commonly diagnosed cancers. Almost ten million colo-rectal cancer deaths occurred in 2020. Existing treatment strategies often led to several off-target and adverse effects. A variety of studies have shown the anti-cancer potential of titanium oxide nanoparticles (TiO2). Therefore, in this study, we have synthesized TiO2 using Lactobacillus and its cytotoxic potential has been evaluated in HT-29 cells, a human CRC cell line. The morphology of TiO2 nanoparticles was analyzed by scanning electron microscope. The cytotoxicity was investigated by MTT assay. Apoptosis-related morphology was analyzed by acridine orange/ethidium bromide staining. Mitochondrial health was analyzed by rhodamine staining. Caspase 3 was analyzed by immunofluorescence. Lactobacillus mediated TiO2 treatments induced cytotoxicity in HT-29 cells. These nanoparticles also induced intracellular reactive oxygen species (ROS) generation and caused apoptosis-related morphological changes in colon cancer cells. TiO2 treatments decreased bcl-2 and increased bax, apaf-1, caspase-9 and −3 gene expressions and this treatment also caused mitochondrial dissipation and cytochrome c release. The current study results suggest that TiO2 is capable of inducing cytotoxicity in colon cancer cells by intracellular ROS accumulation. The ROS induction was associated with mitochondrial toxicity and cytochrome c increase can be related to the induction of intrinsic apoptosis. These results indicate that TiO2 could cause apoptosis by activating intrinsic apoptotic pathway and generating ROS in HT-29 cells. These results suggest that TiO2 can be used as a lung cancer therapeutic agent after necessary in vivo and clinical studies.