Seda Nur Özbolat1, Adnan Ayna1. 1. Department of Chemistry, Faculty of Arts and Sciences, Bingol University, Bingol, Turkey.
Abstract
BACKGROUND: Diclofenac (Dic) was shown to increase in reactive oxygen species (ROS) levels thereby resulting oxidative stress and apoptotic cell death in colon cancer. The antioxidants can prevent and repair oxidative damage caused by ROS. The aim of this study was to assess the effect of chrysin (Chr) on Dic-induced toxicity in HT-29 and molecular mechanisms underlying its effect. METHODS: Cell proliferation and cytotoxicity assays were carried out by WST-1 and LDH leakage assay, apoptotic index was calculated by TUNEL Assay, antioxidant parameters were studied by measurement of ROS, LPO and TAS levels and catalase activity, expression of caspase-3 protein levels were analyzed by immunohistochemical staining, mRNA levels of apoptotic and anti-apoptotic genes were studied by qRT-PCR. RESULTS: The cellular processes of Dic-triggered cell death was associated with increase in ROS, malondialdehyde levels and lactate dehydrogenase release, decrease in total antioxidant and catalase activity while pretreatment with Chr reversed these effects. The expression level of p53, cas-3, cas-8, Bax and cytochrome c increased in Dic-exposed group while they were reduced by Chr. CONCLUSION: The use of antioxidant nutritional supplements, and in particular of Chr, may reduce the efficacy of Dic in inducing apoptosis of colon cancer cells.
BACKGROUND:Diclofenac (Dic) was shown to increase in reactive oxygen species (ROS) levels thereby resulting oxidative stress and apoptotic cell death in colon cancer. The antioxidants can prevent and repair oxidative damage caused by ROS. The aim of this study was to assess the effect of chrysin (Chr) on Dic-induced toxicity in HT-29 and molecular mechanisms underlying its effect. METHODS: Cell proliferation and cytotoxicity assays were carried out by WST-1 and LDH leakage assay, apoptotic index was calculated by TUNEL Assay, antioxidant parameters were studied by measurement of ROS, LPO and TAS levels and catalase activity, expression of caspase-3 protein levels were analyzed by immunohistochemical staining, mRNA levels of apoptotic and anti-apoptotic genes were studied by qRT-PCR. RESULTS: The cellular processes of Dic-triggered cell death was associated with increase in ROS, malondialdehyde levels and lactate dehydrogenase release, decrease in total antioxidant and catalase activity while pretreatment with Chr reversed these effects. The expression level of p53, cas-3, cas-8, Bax and cytochrome c increased in Dic-exposed group while they were reduced by Chr. CONCLUSION: The use of antioxidant nutritional supplements, and in particular of Chr, may reduce the efficacy of Dic in inducing apoptosis of colon cancer cells.
Authors: Behçet Varışlı; Cuneyt Caglayan; Fatih Mehmet Kandemir; Cihan Gür; İbrahim Bayav; Aydın Genç Journal: Mol Biol Rep Date: 2022-09-03 Impact factor: 2.742