Human Seminal Plasma Kills Human Epithelial Ovarian Cancer Cells via Induction of Necrosis

Park, Lae Ok; Kim, Jae Hoon; Lee, Sung Jong; Seo, Ju Tae; Kim, Jae Dong; Lee, Youn Soo; Kim, Byung Kee; Bae, Seog Nyeon

Abstract

OBJECTIVE
From knowledge of risk factors of epithelial ovarian cancer, we deduced a hypothesis that a reduced exposure to human seminal plasma (hSP) during the period of ovulation is one of etiological risk factors in the development of epithelial ovarian cancer and hSP contribute to eliminate maltransformed epithelial cells. MATERIALS & METHODS: To examine whether hSP directly influence the growth of ovarian cancer, we have been investigated the in vivo and in vitro effects of hSP on epithelial ovarian cancer cells (SK-OV-3, OVCAR-3) and, as a control, we also tested its effect in cervical cancer cell (CaSki) and fibroblast cell (WI-38). In in vitro MTT assays of ovarian cancer cells, we found hSP induces necrosis at a final concentration of 1:50 dilution, whereas cervical cancer cell and fibroblast cell were not affected. The flowcytometric assay, DNA laddering, biochemical assay and morphological analysis indicated that hSP induced necrosis rather than apoptosis of both ovarian adenocarcinoma cell lines. The morphological alterations of hSP-treated SK-OV-3 cells were confirmed by transmission electron microscopy that demonstrated swollen mitochondrias with partially or completely destroyed cristae and shrinkage of nucleus with margination and condensation of chromatin, and intranuclear vesiculation. These findings strongly suggest that hSP induced necrosis of ovarian cancer cell lines through destruction of mitochondria. In in vivo experiments that used the nude mice (Balb-C) with tumor by inoculation of SK-OV-3 ovarian cancer cell line, hSP induced necrosis of tumor with no detectable toxic effects on the major organs.
CONCLUSION
Our study supported the hypothesis that hSP has a potent cytotoxic effect on epithelial ovarian cancer cells. Therefore, hSP can be used as a safe, promising therapeutic agent for the epithelial ovarian cancer and may provide a scientific basis for preventing epithelial ovarian cancer by direct exposure to seminal plasma without barrier and withdrawal method for contraception.