Pretreatment with Cilostazol Attenuates Carboplatin Induced Cytotoxicity and Genotoxicity in Bronchial Epithelial Cells (Beas-2B) and Human Blood Lymphocytes

Abstract

Background and purpose: Cilostazol is a prescription medication for intermittent claudication in patients with peripheral artery disease. Previous research has demonstrated that this 2-oxoquinoline derivative possesses antithrombotic, vasodilator, antimitogenic, and antioxidant effects. Cilostazol exerts its products through the inhibition of PDE3 activity and the prevention of cAMP degradation. The present study aimed to examine the protective properties of cilostazol against carboplatin-induced cytotoxicity and genotoxicity in Beas-2B and human blood lymphocyte cells. Materials and methods: cells were pre-treated with different concentrations of cilostazol (5, 25, 50, and 100 μM) with carboplatin at an optimum cytotoxic dosage (9.2 µM). The MTT and micronucleus assays were used to assess cytotoxicity and genotoxicity. Statistical analysis was performed using the one-way ANOVA in Prism Ver. 8 software. Results: The cytotoxic effect of carboplatin was dose-dependent, as evidenced by the 48h culture treatment with concentrations of 0.3, 1, 3, 10, and 30 µM. Pre-treatment of cilostazol at 25, 50, and 100 µM with carboplatin at 9.2 µM enhanced cell viability in Beas-2B cells compared to the carboplatin alone as positive control. Additionally, cilostazol at 50 and 100 µM showed its potent genoprotective effects via micronucleus assay against carboplatin at IC50 at blood lymphocyte cells. Conclusion: Cilostazol provided conceivable protective effects by modulating cytotoxicity and genotoxicity induced by carboplatin in Beas-2B and human blood lymphocyte cells.

Keywords

• cilostazol
• carboplatin
• micronucleus assay
• cytotoxicity