Treatment of malignant melanoma (melanoma malignum) is still challenging because of its aggressiveness, rapid development and resistance to therapy. Melanoma malignum is a tumor originated from the melanocytes, pigment cells differentiated from neural crest. Mammalian melanocytes synthesize  two types of the melanin, black to brown eumelanin and yellow to red-brown pheomelanin, that gives color to skin and hair. Synthesis and accumulation of the melanin in malignant melanoma cells is a crucial factor that influences the effectiveness of therapy. It is believed that melanin hinders the radiotherapy and photodynamic therapy of melanoma. Moreover, melanin, binding with cytostatics , decreases the efficacy of melanoma chemotherapy. Therefore, it’s worth to consider the influence of melanin to the melanoma resistance to the treatment, and to investigate the melanin as a possible target of the chemotherapy.

o-Semiquinone free radicals with spin S = ½ [1-3] and biradicals with spin S = 1 [2] exist in melanin. Paramagnetic centers of melanin take a part in complex formation of this polymer with drugs [2-3].

In this work the effect of valproid acid (VPA) and cisplatin (CPT) on free radical properties of melanin isolated from A-375 cells was studied by the use of electron paramagnetic resonance (EPR) spectroscopy.

The measurements were performed by an X band (9.3 GHz) EPR spectrometer of Radiopan Firm (Poznań, Poland) and the Rapid Scan Unit of Jagmar Firm (Kraków, Poland). The first-derivative EPR spectra of melanin isolated from A-375 cells treated with VPA, CPT, and both VPA and CPT, were analysed. Amplitudes (A), integral intensities (I), linewidths (ΔB_pp), and g-factors were compared. Free radicals concentrations in the melanin samples were determined. Changes of the EPR parameters with increasing of microwave power in the range of 0.7-70 mW were examined. Spin-lattice and spin-spin interactions in the melanin samples were compared. It was shown that CPT and VPA change the parameters of the EPR spectra of melanin and they influence the free radicals concentration in melanin. It was shown that the EPR method may be used in the tests for clinical applications of the antitumor drugs. The performed spectroscopic studies broaden the knowledge about paramagnetic centers in melanin-drug complexes and they role in drug binding to melanin in human melanoma malignum tumor cells.

References

1. Sarna T. (1981). Badanie struktury i właściwości centrów aktywnych melanin. Zagadnienia Biofizyki Współczesnej, Vol.6, pp. 201-219.
2. Kozdrowska L. (2006). Właściwości centrów paramagnetycznych kompleksów DOPA-melaniny z kanamycyną i jonami miedzi(II), Rozprawa doktorska. Uniwersytet Zielonogórski, Zielona Góra.
3. Buszman E., Pilawa B., Zdybel M., Wrześniok D., Grzegorczyk A., Wilczok T. (2005). EPR examination of Zn2+ and Cu2+ effect on free radicals in DOPA-melanin-netilmicin complexes. Chemical Physics Letters, Vol.403, No.1-3, pp. 22-28.

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