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The Effect Of Alkylphosphocholines On Melanoma Cells In Vitro

Dimitrova, V.S. (Dept. Pharmacol. Toxicol., Medical University, Bulgaria)
Lolov, S.R.. (Dept Molec. Immunol., Bulgarian Academy of Science, Bulgaria)
Kyurkchiev, S.D. (Dept. Molec. Immunol.,Bulgarian Academy of Science, Bulgaria)
Karaivanova, M.H. (Dept. Pharmacol. Toxicol., Medical University, Bulgaria)

Contact Person: Stephan R. Lolov (lolov@mont.nbu.acad.bg)


PROBLEM: Alkylphosphocholines (APC) are a new class of antitumor drugs with just a limited clinical use for local treatment of breast cancer skin metastases. The aim of this study was to test the effect of APC on some melanomas as a model system for solid tumors. METHODS: Three melanoma cell lines were tested in vitro - SK-MEL-1, SK-MEL-5 and B16-F1, as well as T-lymphoma Jurkat and promonocytic U-937. The effect of three members of APC family - HPC, ODPP and EPC3 have been proved. A combination of HPC with cisplatin has been used to look for some synergism. The antitumor effects were assessed with MTT-assay, DNA gel electrophoresis and light microscopy. RESULTS: When B16-F1 was treated for 48 h, HPC, ODPP and EPC3 have approximately equal IC50 values - 80 uM, 93 uM and 104 uM respectively. Similar IC50 values have been obtained for two SK-MEL lines. In contrast cell lines with blood origin - Jurkat and U-937 were much more sensitive to a treatment with APC - IC50 values were 3 to 5 times lower. A combination of HPC with cisplatin has been tested, but the results were no better than the separate application of both drugs. Morphologic changes dependent of the dosis applied have been observed after exposure of B16 melanoma cell line with HPC - vacuolization, incomplete adhesion, rounded appearance. There were no condensation of the cytoplasm and nucleus. Agarose gel electrophoresis didn't reveal apoptosis-like oligonucleosomal fragmentation, but simple DNA degradation. CONCLUSIONS: From the three APC tested HPC shows the strongest cytotoxicity. However melanoma cell lines are much more resistant in vitro in comparison to lines of blood origin. Combined application of HPC and Cisplatin does not lead to better cytotoxic effect. Morphological changes and electrophoretical results suspected membrane alteration but no induction of apoptosis to be the citotoxic mechanism of APC.

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Poster Number PAdimitrova0655
Keywords: melanoma, alkylphosphocholi, APC, HPC

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Dimitrova, V.S.; Lolov, S.R..; Kyurkchiev, S.D.; Karaivanova, M.H.; (1998). The Effect Of Alkylphosphocholines On Melanoma Cells In Vitro. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Available at URL http://www.mcmaster.ca/inabis98/cancer/dimitrova0655/index.html
© 1998 Author(s) Hold Copyright