Folic acid enhances the apoptotic and genotoxic activity of carboplatin in HeLa cell line

• Published in: Toxicology in vitro 2016-12, Vol.37, p.142-147
• Main Authors: Nikoloff, N., Ponzinibbio, M.V., Padula, G., De Luca, J.C., Golijow, C.D., Seoane, A.
• Format: Article
• Language: English
• Subjects: Annexin V; Antineoplastic Agents - toxicity; Apoptosis; Apoptosis - drug effects; Bioassays; Biological activity; Biological effects; Carboplatin; Carboplatin - toxicity; CBMN-cyt assay; Cell death; Cervical carcinoma; Cervix; Chemotherapy; Chromosome aberrations; Comet Assay; Cytokinesis; Cytotoxicity; Damage detection; Deoxyribonucleic acid; DNA; DNA Damage; Drug Synergism; Folic acid; Folic Acid - pharmacology; Genotoxicity; HeLa Cells; Humans; Micronucleus Tests; Mitosis - drug effects; MTT assay; Mutagens - toxicity; Platinum; Platinum compounds; Side effects; Toxicity; Transduction; Tumor cells; Vitamin B
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2016.09.019

In human tumor cells, experimental and clinical evidence indicates that some factors involved in signal transduction and cell growth can also modulate the response to chemotherapeutic treatment. The aim of the present study was to investigate the role of folic acid (FA) as a modulator of carboplatin (CBDCA) activity. Genotoxicity and cytotoxicity induced by CBDCA alone and in combination with FA were assessed in cultured HeLa cells. We used comet assay, mitotic index analysis, MTT and NR assays, cytokinesis-block micronucleus cytome assay and annexin V-IP as different cytotoxicity and genotoxicity approaches for human cervical carcinoma cell line studies. The results showed that addition of 900nM FA together with 40.4mM CBDCA enhanced the activity of the platinum compound, increasing its effect on cell death by nearly 20%, as evidenced by the MTT and NR assays. Moreover, not only higher levels of DNA and chromosomal damage were reached but also the number of necrotic and apoptotic cells were significantly increased when cell cultures were treated with the combined procedure. This situation opens the possibility to explore the use of FA in platinum-based chemotherapy protocols to reduce the platinum doses for patient treatment and decrease the chance of developing the known side effects without losing biological activity. [Display omitted] •Addition of folic acid enhanced the genotoxic and apoptotic activity of carboplatin.•The use of folic acid in carboplatinum therapy allows reducing the platinum dose.•Folic acid could work as a modulator of carboplatin activity in vitro.•Folic acid could form spontaneous complexes with carboplatin for entering to the cell.