Oxidative stress induced by carboplatin promotes apoptosis and inhibits migration of HN‑3 cells

Abstract

Laryngeal squamous cell carcinoma (LSCC) is currently a serious public health problem in China; thus, it is urgent to identify effective treatment strategies for this disease. Previous studies demonstrated that reactive oxygen species (ROS) serve important roles in the apoptosis of LSCC cells. It has also been indicated that carboplatin (CBDCA), a second-generation platinum compound with broad antineoplastic properties, is able to induce oxidative stress to produce ROS, which in turn promotes apoptosis. Thus, the present study investigated if CBDCA is cytotoxic in LSCC cells due to the oxidative stress caused by ROS. Therefore, an MTT assay was performed to determine the cell viability of HN-3 LSCC cells following treatment with different doses of CBDCA. Subsequently, the expression levels of ROS and the rate of apoptosis/necrosis were evaluated in the cells. Following this, the HN-3 cells were co-treated with CBDCA and glutathione (GSH) or H2O2, followed by an MTT assay, a cell migration assay and western blot analysis. The results demonstrated that CBDCA reduced the viability of HN-3 cells in a time- and dose-dependent manner and promoted the production of ROS and apoptosis at certain doses. Additionally, the combination treatment of CBDCA and H2O2 enhanced the inhibitory effects of CBDCA on cell viability and migration ability, and promoted apoptosis in HN-3 cells; whereas the combined treatment of CBDCA and GSH exerted opposite effects. The results of the present study demonstrated that CBDCA promotes the apoptosis of HN-3 cells through accumulation of ROS, which may provide a novel treatment strategy for treating LSCC.

Targeting Glutathione and Cystathionine β-Synthase in Ovarian Cancer Treatment by Selenium–Chrysin Polyurea Dendrimer Nanoformulation

“…Ovarian cancer is not an exception, and carboplatin is applied as a neoadjuvant, adjuvant, and palliative therapy, alone or combined with taxanes [1,7,8]. The mechanisms of action of platinum drugs are based on the establishment of adducts of DNA and proteins along with the generation of intracellular reactive oxygen species (ROS), leading to cell injury and death [9,10]. Chemoresistance against oxidative/alkylating drugs is associated with alterations in glutathione (GSH) and cysteine dynamics, as well as in cystathionine β-synthase (CBS)-catalyzed hydrogen sulfide (H 2 S) biosynthesis [9,11,12].…”

Chemoradiation induces epithelial‐to‐mesenchymal transition in esophageal adenocarcinoma

“…For instance, numerous factors are known to activate latent TGF‐β, including reactive oxygen species . Studies have described the generation of reactive oxygen species in tumor cells by treatment with either paclitaxel, carboplatin or radiotherapy, and this could explain the induction of active TGF‐β after this combination regimen . TGF‐β production could also be regulated by changes in microRNA expression.…”

“…31 Studies have described the generation of reactive oxygen species in tumor cells by treatment with either paclitaxel, carboplatin or radiotherapy, and this could explain the induction of active TGF-β after this combination regimen. [32][33][34] TGF-β production could also be regulated by changes in micro-RNA expression. Several microRNAs have been shown to regulate TGF-β synthesis and various types of treatments or environmental changes have been described to affect microRNA expression.…”

Molecules and Mechanisms to Overcome Oxidative Stress Inducing Cardiovascular Disease in Cancer Patients

“…The mechanisms underlying carboplatin-mediated cardiovascular toxicity are still unclear. It is shown that ROS production and oxidative stress are also implicated [ 56 ].…”