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Effect of valproic acid and cisplatin on the proliferation of tumor cell lines A375 and C32

Ewa Chodurek 1Arkadiusz Orchel 1Arkadiusz R. Gruchlik 1Ewelina Aleksander 1Karolina Gołąbek 2Zofia Dzierżewicz 1

1. Department of Biopharmacy, Medical University of Silesia, Narcyzów 1, Sosnowiec 41-200, Poland
2. Chair and Department of General Biology, Medical University of Silesia, Jordana 19, Zabrze 41-800, Poland

An early diagnosis, in the initial phase of development of melanoma malignum, increases  the chance of complete recovery, whereas the advanced stage of melanoma is almost fully resistant to all available therapies. Surgical removal of the lesion is the primary method of melanoma regimen, whereas radio-, chemo- and immunotherapy are a supplementary treatment. From among platinum – based chemotherapeutic drugs, cisplatin (cis-diamminedichloroplatinum, CPT) was the first used in treatment of melanoma. However, CPT has a low efficacy in therapy of melanoma, which is associated with cell resistance to this drug, and high toxicity. For this reason, novel therapeutic strategies are sought (analogues of cisplatin). A new promising group of compounds used in the therapy of melanoma are histone deacetylase (HDAC) inhibitors. One of them is valproic acid (2-propylpentanoic acid, VPA) which undergoes phase I and II clinical trials.

The aim of our study was to evaluate the influence of valproic acid and cisplatin on morphology and growth rate in human melanoma cell lines: A375 (melanotic) and C32 (amelanotic). Cell proliferation was measured using sulforhodamine B (In Vitro Toxicology Assay Kit, Sigma-Aldrich), a dye binding to cellular proteins.

Our results suggest that CPT and VPA exerted synergistic inhibitory effect on the growth of both studied cell lines. Cisplatin alone inhibited the cell growth at concentrations ≥0.3 μM. Inhibitory effect of valproic acid was seen at concentrations ≥1 mM. However, the combination of both compounds displayed the strongest cytotoxic effect.


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Submitted: 2012-03-12 08:42
Revised:   2012-03-19 07:44