An In Vitro Study on the Interactions of Pycnogenol ^® with Cisplatin in Human Cervical Cancer Cells

Objectives: In the treatment of cancer, it is intended to increase the anticancer effect and decrease cytotoxicity using various plant-derived phenolic compounds with chemotherapeutic drugs. Pycnogenol^® (PYC), a phenolic compound, has been the subject of many studies. Since the mechanisms of the interactions of PYC with cisplatin need to be clarified, we aimed to determine the effects of PYC on cisplatin cytotoxicity in human cervix cancer cells (HeLa) and to evaluate the genotoxicity of PYC.

Materials and methods: The cytotoxicity of cisplatin and PYC was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in HeLa cells for 24 h and 48 h. The effect of PYC against oxidative DNA damage was evaluated using the comet assay.

Results: The IC₅₀ values of cisplatin were 22.4 μM and 12.3 μM for 24 h and 48 h, respectively. The IC₅₀ values of PYC were 261 μM and 213 μM for 24 h and 48 h, respectively. For 24 h exposure, PYC significantly reduced the IC₅₀ value of cisplatin at the selected concentrations (15.6-500 μM). For 48 h exposure, PYC did not change the cytotoxicity of cisplatin at concentrations between 15.6 and 125 μM, but significantly reduced it at concentrations of 250 μM and 500 μM. PYC alone did not induce DNA damage at concentrations of 10 μM or 25 μM; however, it significantly induced DNA damage at higher concentrations (50-100 μM). It also significantly reduced H₂O₂-induced DNA damage at all concentrations studied (10-100 μM).

Conclusion: Our results suggest that PYC may increase the cisplatin cytotoxicity in HeLa cells at nongenotoxic doses. The results might contribute to the anticancer effect of cisplatin with PYC in cervical carcinoma, but in order to confirm this result further in vitro studies with cancer cell lines and in vivo studies are needed.

Keywords: Pycnogenol; cisplatin; cytotoxicity; genotoxicity; human cervix cancer cells.