Abstract

A membrane-targeted, lipophilic ether lipid of synthetic phospholipid analog, erucylphosphocholine (ErPC) induces apoptosis in some lines of human tumor cells. We investigated the effect of ErPC on three endometrial cancer cell lines, two ovarian cancer cell lines, and normal human endometrial epithelial cells. Endometrial and ovarian cancer cells were treated with various concentrations of ErPC, and its effect on cell growth, cell cycle, apoptosis, and related measurements was investigated. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that all endometrial and ovarian cancer cell lines were sensitive to the growth-inhibitory effect of ErPC, although normal endometrial epithelial cells were viable after treatment with the same doses of ErPC that induced growth inhibition in endometrial and ovarian cancer cells. Cell cycle analysis indicated that their exposure to ErPC decreased the proportion of cells in the S-phase and increased the proportion in the G2/M phases of the cell cycle. Induction of apoptosis was confirmed by annexin V staining of externalized phosphatidylserine and loss of the transmembrane potential of mitochondria. This induction occurred in concert with altered expression of genes related to cell growth, malignant phenotype, and apoptosis. These results suggest that the anticancer activity of ErPC may occur with higher sensitivity of cancer cells compared with normal healthy cells, when using low concentration, rising hopes that ErPC may become a useful adjuvant therapy for endometrial and ovarian cancers.

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