Antiproliferative Activity of Ceramides Isolated from Normal Human Ovary and Ovarian Tumor

S. N. Rylova,¹ A. M. Kozlov,² L. S. Kogtev,¹ G. P. Gaenko,¹ and E. V. Dyatlovitskaya^1,3

¹Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow, 117871 Russia; fax: (7-095) 335-7103.

²Institute of Experimental Diagnostics and Therapy of Tumors, Oncology Research Center, Russian Academy of Medical Sciences, Kashirskoe Shosse 24, Moscow, 115478 Russia.

³To whom correspondence should be addressed.

Submitted May 12, 1997; revision submitted May 26, 1997.

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Ceramides modulate cell growth, differentiation and apoptosis. We have previously demonstrated that human epithelial ovarian tumors contain dihydroceramides that are absent from normal ovary. Dihydroceramides differ in their biological effects from ceramides; thus, antiproliferative activity of ceramides isolated from normal human ovary and ovarian tumors was studied. Ceramides (3 µM) of normal ovary are more potent inhibitors of [³H]thymidine incorporation into human ovarian carcinoma cells (CaOv) than ceramides of ovarian tumors. Effects of various pools of tumor ceramides were similar regardless of significant differences in the contents of sphingenine and sphinganine. It is suggested that antiproliferative activity of ceramides depends not only on the sphingoid base structure but also on the fatty acid structure.

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KEY WORDS: antiproliferative activity, ceramide, cytotoxicity, sphingoids, fatty acid, tumor, human ovary.

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