Folic acid enhances the apoptotic and genotoxic activity of carboplatin in HeLa cell line.
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.
IGEVET, Instituto de Genética Veterinaria "Ing. Fernando N Dulout"(UNLP-CONICET-CONICET LA PLATA), Facultad de Ciencias Veterinarias - UNLP, Calle 60 118, B1904AMA La Plata, Buenos Aires, Argentina. Electronic address: noenik_@hotmail.com.
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Nikoloff
IGEVET, Instituto de Genética Veterinaria "Ing. Fernando N Dulout"(UNLP-CONICET-CONICET LA PLATA), Facultad de Ciencias Veterinarias - UNLP, Calle 60 118, B1904AMA La Plata, Buenos Aires, Argentina.
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Ponzinibbio
IGEVET, Instituto de Genética Veterinaria "Ing. Fernando N Dulout"(UNLP-CONICET-CONICET LA PLATA), Facultad de Ciencias Veterinarias - UNLP, Calle 60 118, B1904AMA La Plata, Buenos Aires, Argentina.
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Padula
IGEVET, Instituto de Genética Veterinaria "Ing. Fernando N Dulout"(UNLP-CONICET-CONICET LA PLATA), Facultad de Ciencias Veterinarias - UNLP, Calle 60 118, B1904AMA La Plata, Buenos Aires, Argentina.
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JC
De Luca
IGEVET, Instituto de Genética Veterinaria "Ing. Fernando N Dulout"(UNLP-CONICET-CONICET LA PLATA), Facultad de Ciencias Veterinarias - UNLP, Calle 60 118, B1904AMA La Plata, Buenos Aires, Argentina.
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Golijow
IGEVET, Instituto de Genética Veterinaria "Ing. Fernando N Dulout"(UNLP-CONICET-CONICET LA PLATA), Facultad de Ciencias Veterinarias - UNLP, Calle 60 118, B1904AMA La Plata, Buenos Aires, Argentina.
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Seoane
D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D016190:Carboplatin / Q000633:toxicity*; D020552:Comet Assay; D004249:DNA Damage; D004357:Drug Synergism; D005492:Folic Acid / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D015162:Micronucleus Tests; D008938:Mitosis / Q000187:drug effects; D009153:Mutagens / Q000633:toxicity*
D000970:Antineoplastic Agents; D009153:Mutagens; D005492:Folic Acid; D016190:Carboplatin
CBMN-cyt assay; Carboplatin; Comet assay; Folic acid; HeLa cells; MTT assay