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

NIKOLOFF, N; PONZINIBBIO MV; PADULA G; DE LUCA JC; GOLIJOW C; SEOANE A

TOXICOLOGY IN VITRO : AN INTERNATIONAL JOURNAL PUBLISHED IN ASSOCIATION WITH BIBRA.

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2016

0887-2333

In human tumor cells, experimental and clinical evidence indicates that some factors involvedin signal transduction and cell growth can also modulate the response to chemotherapeutictreatment. The aim of the present study was to investigate the role of Folic Acid (FA) as amodulator of Carboplatin (CBDCA) activity.Genotoxicity and cytotoxicity induced by CBDCA alone and in combination with FA wereassessed in cultured HeLa cells. We used comet assay, mitotic index analysis, MTT and NRassays, cytokinesis-block micronucleus cytome assay and annexinV-IP as differentcytotoxicity and genotoxicity approaches for human cervical carcinoma cell line studies.The results showed that addition of 900 nM FA together with 40.4 mM CBDCA enhanced theactivity of the platinum compound, increasing its effect on cell death by nearly 20%, asevidenced by the MTT and NR assays. Moreover, not only higher levels of DNA andchromosomal damage were reached but also the number of necrotic and apoptotic cells weresignificantly increased when cell cultures were treated with the combined procedure.This situation opens the possibility to explore the use of FA in platinum-based chemotherapyprotocols to reduce the platinum doses for patient treatment and decrease the chance ofdeveloping the known side effects without losing biological activity.