TURK 2025

The overproduction of cyclooxygenase-2 (COX-2) has been linked to the development of liver cancer. A series of compounds, including Azaspiro[3,4]octane-1-one and Arylpyrrole derivatives, were designed and synthesized for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors and for their anti-tubulin effects. Evaluation of the cytotoxic effects of Azaspiro [3,4] octane-1-one and Arylpyrrole compounds on hepatocytes derived from the livers of rats with hepatocellular carcinoma (HCC) involves assessing their impact on mitochondrial function via reactive oxygen species (ROS) mediated targeting. This study investigated HCC caused by exposure to diethylnitrosamine (DEN) and 2-acetylaminofluorene (2-AAF). Rat liver hepatocytes and mitochondria were isolated and evaluated for any potential anti-apoptotic and anti-HCC effects of Azaspiro [3,4]octane -1-one and Arylpyrrole compounds. The MTT assay results demonstrated that Azaspiro [3,4]octane -1-one and Arylpyrrole compounds caused selective cytotoxicity in the liver cells of the HCC group in a manner that depended on both the dose and the amount of time..Treatment of mitochondria from liver cancer cells with Azaspiro [3,4]octane -1-one and Arylpyrrole compounds resulted in a loss of mitochondrial membrane potential (MMP) and swelling, as well as the release of cytochrome c (P < 0.001), which occurred prior to cytotoxicity through the generation of reactive oxygen species (ROS).. Azaspirooctane-1-one and Arylpyrrole compounds were also found to increase the activation of caspase-3, with statistically significant results achieved at P < 0.001 and P < 0.01, respectively [3,4]. Results from flow-cytometry analysis showed that the primary mode of cell death caused by these compounds was apoptosis. Azaspiro [3,4] octane-1-one and Arylpyrrole compounds exhibited no toxicity toward normal liver cells and mitochondria. We propose that Azaspiro [3,4] octane -1-one and Arylpyrrole compounds serve as a suitable candidate for use as complementary therapeutic agents for treating HCC.