Toxicity of Synthesized Ciprofloxacin Conjugated Peptide in Colorectal Carcinoma Cells

IntroductionCancers of the colon and rectum are the most common gastrointestinal neoplasms, with an incidence of about 44 per 100 000 per year. Anticancer peptides offer the possibility of efficient anticancer drugs potency. Ciprofloxacin, a broad-spectrum antibiotic of the fluoroquinolone class, works by inhibiting bacterial DNA gyrase and topoisomerase IV, which are required for DNA synthesis. It has been reported that ciprofloxacin inhibit cell growth and induced apoptosis in certain eukaryotic cells including bladder tumor cells. In one research, it has been shown that ciprofloxacin induces growth inhibition and apoptosis in colon carcinoma cell lines. Therefore ciprofloxacin can be used as an anticancer peptides. In this study, we investigate the effects of ciprofloxacin conjugated peptides in isloated rat colon carcinoma mitochondria.Materials and methods: Wang resin was used for constructing peptide sequence on solid support using the method of solid phase peptide synthesis with the fmoc stategy. The colorectal carcinoma animal models were purchased and used for obtaining mitochondria. Cytotoxicity of the synthesized peptide compounds was evaluated by MTT reduction. Mitochondrial ROS formation in isolated rat colon mitochondria was measured using DCFH-DA. Mitochondrial swelling was estimated by alterations of the light scattered from mitochondrial suspension. The malonyl dialdehyde levels in mitochondria was determined by measuring the formation of TBARS according to Buege and Aust. ATPase activity was determined by the method of Lardy and Wellman. Caspase-3 activity measured colorimetrically using the Sigma caspase-3 assay kit. Data are presented as mean ± SD. Experimental tests were performed in triplicate. All statiscal analyses were performed using the Graph pad prism software, version 6.Results: Our results show significant decrease in activity of complex II. Ciprofloxacin conjugated peptide compounds significantly increase ROS production, mitochondrial swelling, lipid peroxidation, caspase-3 activity. ATP depletion was occurred after incubation of mitochondria with ciprofloxacin conjugated peptide.Discussion: According to our results, ciprofloxacin conjugated peptide compounds inhibit cell growth by mitochondrial dysfunction in colon carcinoma cell.

کلیدواژه ها:

Ciprofloxacin ، Colon carcinoma ، Conjugated peptide ، Mitochondria ، Toxicity