Arsenic trioxide induces apoptosis and the formation of reactive oxygen species in rat glioma cells

Abstract

BackgroundArsenic trioxide (As2O3) has a dramatic therapeutic effect on acute promyelocytic leukemia (APL) patients. It can also cause apoptosis in various tumor cells. This study investigated whether As2O3 has an antitumor effect on glioma and explored the underlying mechanism.ResultsMTT and trypan blue assays showed that As2O3 remarkably inhibited growth of C6 and 9 L glioma cells. Cell viability decreased in glioma cells to a greater extent than in normal glia cells. The annexin V-FITC/PI and Hoechest/PI staining assays revealed a significant increase in apoptosis that correlated with the duration of As2O3 treatment and occurred in glioma cells to a greater extent than in normal glial cells. As2O3 treatment induced reactive oxygen species (ROS) production in C6 and 9 L cells in a time-dependent manner. Cells pretreated with the antioxidant N-acetylcysteine (NAC) showed significantly lower As2O3-induced ROS generation. As2O3 significantly inhibited the expression of the anti-apoptotic gene Bcl-2, and upregulated the proapoptotic gene Bax in both C6 and 9 L glioma cells in a time-dependent manner.ConclusionsAs2O3 can significantly inhibit the growth of glioma cells and it can induce cell apoptosis in a time- and concentration-dependent manner. ROS were found to be responsible for apoptosis in glioma cells induced by As2O3. These results suggest As2O3 is a promising agent for the treatment of glioma.

Arsenic trioxide as a novel anti-glioma drug: a review

“…This change is related to the mitochondrial damage caused by the production of intracellular ROS. However, the inhibition rate for normal rat glial cells was less than 10% of that for rat glioma cells [ 42 ].…”

A novel RGDyC/PEG co-modified PAMAM dendrimer-loaded arsenic trioxide of glioma targeting delivery system

“…9,10 Interestingly, some studies have shown that ATO could also inhibit growth and induce apoptosis in a variety of solid tumor cells, such as breast, liver, gastric, prostate, renal, bladder, and glioma cells. [10][11][12][13][14] However, several limitations hinder its applications in clinical practice. The free ATO in aqueous solution exists as arsenite ions, with fast elimination in vivo, poor pharmacokinetics, and unacceptable systemic toxicity, including peripheral neuropathies and liver failure.…”

Nickel Nanoparticles Induced Nephrotoxicity in Rats: Influence of Particle Size

“…The Immunohistochemical demonstration of p53 positive cells has confirmed that the main mode of NiNPs-cell death was the programmed cell death, particularly apoptosis. When the damage in the gene is too sever and couldn't be repaired by it's own cell, the induction of apoptosis by p53 is processed (Wawryk-Gawda et al, 2014).The significant increase in the number of p53 positive kidney tubular cells in the NiNPs treated rats indicates the increased apoptosis mode of cell death, while the size-dependent difference may be related to the induced oxidative stress since oxidative stress is one of the important factors that are known to induce apoptosis (Sun et al, 2018). However, the smallest NiNPs size showed higher p53 positive cells than the other two larger sizes.…”