Anticancer and Anti-inflammatory Effects of Benzothiazole Derivatives Targeting NF-κB/COX-2/iNOS in a Hepatocellular Carcinoma Cell LineMuhammed Mehdi Üremiş1, Nuray Üremiş1, Mustafa Ceylan2, Yusuf Turkoz11Department of Medical Biochemistry, Medical Faculty, Inonu University, Malatya, Turkey 2Department of Chemistry, Faculty of Science and Letters, Gaziosmanpaşa University, Tokat, Turkey
INTRODUCTION: Benzothiazole compounds, characterized by their diverse biological and pharmacological properties, have emerged as promising molecules for suppressing cancer cell proliferation and invasion due to their antiproliferative attributes. Prior research from our laboratory revealed that 2-substituted benzothiazole compounds inhibit the proliferation of glioma and cervical cancer cells and induce apoptosis in pancreatic cancer cells. However, there is limited research on the effectiveness of benzothiazoles against hepatocellular carcinoma cells. This study sought to elucidate the anticancer potential of 2-substituted benzothiazole derivatives through their modulation of oxidative stress and inflammation mediators. METHODS: Antiproliferative effects of two-step synthesized 2-substituted benzothiazole derivatives were evaluated on HepG2 cells via MTT assay. Apoptosis induction was assessed using Annexin V/PI staining, cell cycle arrest effects were determined through cell cycle analysis, cell migration was examined via wound healing assay, and mitochondrial membrane damage was quantified using JC-1 staining. Spectrophotometric measurements of TAS, TOS, SOD, total thiol, and native thiol levels expressed cellular redox status. Expression of NF-κB, an inflammatory marker, was assessed by western blot, while inflammation-related COX-2 and iNOS levels were measured using ELISA. RESULTS: This investigation unveiled benzothiazole derivatives' antiproliferative and cytotoxic properties against HepG2 cells. The synthesized compounds exhibited the ability to suppress cell migration and induce apoptosis, mediated by mitochondrial membrane potential loss. Furthermore, these derivatives reduced SOD activity, TAS levels, and dynamic disulfide content. Notably, a decrease in NF-κB protein levels, closely associated with inflammation, was observed, along with a subsequent reduction in downstream effectors COX-2 and iNOS. DISCUSSION AND CONCLUSION: The findings of this study underscore the antiproliferative effects of benzothiazole derivatives in human hepatocellular carcinoma cells, coupled with their anti-inflammatory potential by diminishing NF-κB levels.
Keywords: Benzothiazole, COX-2, inflammation, iNOS, NF-κ,, B, oxidative stress
Corresponding Author: Muhammed Mehdi Üremiş, Türkiye
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