Arsenic trioxide induces the apoptosis and decreases NF‑κB expression in lymphoma cell lines

Abstract

Lymphoma is a type of cancer that develops from certain immune system cells. Arsenic trioxide (ATO) has attracted wide attention owing to its antitumor activities. However, the role of ATO in tumorigenesis and progression remains to be investigated. In the present study, the antitumor function of ATO was investigated in in lymphoma Raji and Jurkat cell lines and the effect of ATO on nuclear factor (NF)-κB expression levels. A Cell Counting kit-8 assay was used to assess cellular proliferation and the degree of cell apoptosis was measured by flow cytometric analysis; these assays demonstrated that ATO inhibited proliferation and promoted the apoptosis of Raji and Jurkat cells in a dose- and time-dependent manner. Western blot analysis revealed that ATO treatment affected the expression of apoptosis-associated proteins by downregulating the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) and upregulating the pro-apoptotic protein Bcl-2-associatedX and the degree of caspase-3 cleavage. In addition, reverse transcription-quantitative polymerase chain reaction and western blot analysis showed that the mRNA and protein expression levels of NF-κB were downregulated significantly following treatment with 2 µM ATO for 24, 48 and 72 h in the two cell lines. Additionally, immunofluorescence staining indicated that NF-κB expression diminished following ATO treatment in a time-dependent manner. These data indicated that ATO inhibited the proliferation of lymphoma cells by inducing cell apoptosis, which may be associated with the inhibition of the NF-κB signaling pathway. The findings of the present study may lay the foundation for developing a personalized medicine strategy using ATO via targeting of the NF-κB signaling pathway in lymphoma.

Ursodeoxycholic Acid Protects Against Arsenic Induced Hepatotoxicity by the Nrf2 Signaling Pathway

“…However, UDCA promoted activity of SOD, CAT and GSH-Px and inhibited levels of MDA, ROS to the best level in hepatocytes, but it was still slightly lower than the Control. Nrf2 knockdown partially abrogated those effect (Zhong et al, 2018). Additionally, we revealed that UDCA promoted the nuclear translocation of Nrf2 and increased the levels of HO-1, NQO-1 in hepatocytes both in vivo and vitro, accompanied by a reduction of As(III)-provoked oxidative stress and subsequent hepatotoxicity.…”

Evaluation of the target genes of arsenic trioxide in pancreatic cancer by bioinformatics analysis

“…ATO is a chemotherapeutic agent of idiopathic function used to treat leukemia that is unresponsive to first-line agents. It is suspected that ATO induces cancer cells to undergo apoptosis (11). In the current study, DrugBank and STITCH tools were used to identify the target genes of ATO.…”

“…Combined treatment with retinoic acid (RA) and ATO has been demonstrated to be curative for the majority of patients with APL (7–9). Furthermore, an increasing number of studies have proven the anti-carcinogenic properties of ATO in different tumors, including in gastric cancer (10), lymphoma (11), bladder cancer (12), head and neck cancer (13), and ovarian cancer (14). Although it has been reported that ATO may inhibit the progression of pancreatic cancer (15), the potential targets and molecular mechanisms of action of ATO remain unclear.…”

Mechanistic effects of arsenic trioxide on acute promyelocytic leukemia and other types of leukemias

“…Several studies have confirmed anti‐inflammatory effects of ATO on leukemia cells through the regulation of pro‐inflammatory factors (Binet & Girard, 2008; Dunoyer‐Geindre et al, 2017; Sharifizadeh et al, 2016; Zhong et al, 2018). Tissue factor (TF) also called platelet tissue factor, factor III, or CD142 which is involved in the clotting process, is highly expressed on the surface of leukocytes in APL.…”

“…Also, ATO inhibits the expression and activity of NF‐ k B within the inhibition of IKK‐mediated I k B phosphorylation. Furthermore, IL‐6, as a protein involved in the proliferation of myeloid cells is suppressed by ATO (Sharifizadeh et al, 2016; Zhong et al, 2018). It has been reported that the enhancement of migration, adhesion, phagocytosis, and degranulation of secretory granules are a result of p38 and/or JNK activation in neutrophils undergoing treatment with ATO.…”