# Evaluation of Anticarcinogenic and Cytotoxic Effects of COX-2 Specific Inhibitors on an Animal Model of Hepatocellular Carcinoma Using Isolated Mitochondria

## TL;DR

This study tests new COX-2 inhibitors on a rat model of liver cancer to see if they can reduce cancer growth by affecting mitochondria.

## Contribution

The study introduces two new COX-2 inhibitors and evaluates their anticarcinogenic effects on HCC via mitochondrial toxicity.

## Key findings

- 4cl-A and 1-naphtyl-C reduced mitochondrial activity and increased free radicals in HCC mitochondria.
- These compounds caused mitochondrial swelling and cytochrome c release in cancerous but not healthy mitochondria.
- The findings suggest potential for these inhibitors in HCC treatment, though clinical trials are needed.

## Abstract

Cancer is regarded as one of the most significant health concerns in the world. Hepatocellular carcinoma (HCC) is a malignancy with high incidence and mortality rates and can lead to death. Cyclooxygenase (COX)-2 is responsible for the development of various cancers, including HCC. Therefore, the use of COX-2 inhibitors can help in the prevention and treatment of cancer.

The present study aimed to synthesize and examine the effect of imidazolium [1,2-a] piperidinium (4cl-A) and benzo [d] imidazo [1,2-b] thiazolium (1-naphtyl-C) compounds as COX-2 inhibitors on the rat model of HCC.

Animals were randomly assigned to control and HCC induction groups. The study duration was 15 weeks. The HCC was induced using DEN (200 mg/kg, ip) at a single dose and 2-AAF (dietary, 0.02% w/w, for 2 weeks). After 15 weeks, the investigation focused on mitochondrial toxicity parameters. One-way and two-way ANOVA statistical tests were used to analyze the data.

The results showed that 4cl-A and 1-naphtyl-C can reduce mitochondrial activity, increase the level of free radicals (ROS), collapse in mitochondrial membrane potential (MMP), cause swelling of mitochondria, and release cytochrome c from HCC mitochondria. While this effect was not observed in healthy mitochondria.

The results of the study indicate that these COX-2 inhibitors, along with selected drugs, can help in the treatment of HCC. However, more clinical studies should be conducted.