Effects of lysophosphatıdıc acıd agaınst cell toxıcıty of some chemotherapy medıcınes whıch are use ın prostate cancer

Prostate cancer is the second most common malignancy among men in the United States, ranking only behind lung cancer. Various chemotherapy protocols are implemented to improve survival and to provide an effective palliative treatment in prostate cancer. Docetaxel, estramustine, mitoxantrone are chemotherapy agents which are used in prostate cancer. Docetaxel is a semisynthetic taxane, a class of anticancer agents. Estramustine, an estradiol nitrogen mustard conjugate, antineoplastic agent. Mitoxantrone, a synthetic anticancer agent, is a member of the anthracenedione class of compounds and was originally designed as a simplified analogue of the anthraquinone containing anthracylines. Lysophosphatidic acid (LPA) is one of the most interesting phospholipid mediators with multiple biological functions in various human diseases. Lysophosphatidic acid secreted by prostate cancer cells as well as the other cancer cells is able to regulate cell proliferation, survival and migration. The aim of this study was to investigate the effects of lysophosphatidic acid against cell toxicity of some chemotherapy agents (docetaxel, estramustine, mitoxantrone) which are used in prostate cancer. For this purpose, optimum dose of LPA was determined in PC3cells. PC3 cells treated with lysophosphatidic acid, docetaxel, docetaxel+LPA, estramustine, estramustine+LPA, mitoxantrone and mitoxantrone+LPA. Lysophosphatidic acid increased cell proliferation. Docetaxel, estramustine and mitoxantrone decreased cell proliferation. Docetaxel+LPA, estramustine+LPA and mitoxantrone+LPA increased cell proliferation compared to docetaxel, estramustine and mitoxantrone treated cells. Lysophosphatidic acid increased colony formation in PC3 cells. Docetaxel, estramustine and mitoxantrone decreased colony formation. Docetaxel+LPA, estramustine+LPA and mitoxantrone+LPA increased colony formation compared to docetaxel, estramustine and mitoxantrone treated cells. It was seen that lysophosphatidic acid blocked docetaxel, mitoxantrone and estramustine-induced apoptosis. Lysophosphatidic acid decreased docetaxel, estramustine and mitoxantrone-induced cytotoxicity and increased cell survival and proliferation. The blocking of lysophosphatidic acid secretion which is highly expressed in cancer cells may enhance the cell killing effects of docetaxel, estramustine and mitoxantrone in prostate cancer treatment. This study suggest that the inhibition of signal pathways of lysophosphatidic acid could improve the treatment of cancers by docetaxel, mitoxantrone, estramustine and possibly other chemotherapeutic agents.Key words: Prostate cancer, lysophosphatidic acid, docetaxel, estramustine, mitoxantrone, apoptosis, cell proliferation.