Necrotic cell death of ovarian adenocarcinoma caused by seminal plasma

Gynecol Oncol. 2004 Jun;93(3):671-9. doi: 10.1016/j.ygyno.2004.02.030.

Abstract

Objective: From the knowledge of risk factors of epithelial ovarian cancer, we deduced a hypothesis that human seminal plasma (HSP) has a preventive role in the development of epithelial ovarian cancer. To examine whether HSP directly influences the growth of ovarian cancer, we have investigated the in vitro and in vivo effect of HSP on ovarian adenocarcinoma cell lines (SK-OV-3 and OVCAR-3) in comparison with its effects on normal ovarian surface epithelial cells (NOSE).

Methods: Cell viability was determined by MTT assay. Cytotoxic effect was evaluated by flow cytometry analysis, by DNA laddering, and by morphological analysis. In vivo therapeutic effect of HSP was evaluated by the subcutaneous inoculation of SK-OV-3 cells in nude mice (BALB-c) model.

Results: HSP at a final concentration of 1:50 induced a time- and dose-dependent inhibition of SK-OV-3 and OVCAR-3 growth, whereas NOSE was not affected. Flow cytometric analysis, DNA laddering, and morphological analysis indicated that HSP induced necrosis, rather than apoptosis, of both ovarian carcinoma cell lines. In in vivo experiment that used the nude mice (Balb-C) with tumor inoculation of SK-OV-3 cells, HSP induced necrosis of tumor with no detectable toxic effects on the major organs.

Conclusion: These results show that HSP inhibits the growth and induces the necrosis of epithelial ovarian cancer cells and suggests that one or more components of HSP may provide a scientific basis for preventing epithelial ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acridine Orange / chemistry
  • Acridine Orange / metabolism
  • Adenocarcinoma / pathology*
  • Animals
  • Cell Division / physiology
  • Cell Line, Tumor
  • DNA Fragmentation
  • Epithelial Cells / pathology
  • Ethidium / chemistry
  • Ethidium / metabolism
  • Female
  • Flow Cytometry
  • Fluoresceins / chemistry
  • Fluoresceins / metabolism
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / metabolism
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microscopy, Fluorescence
  • Necrosis
  • Ovarian Neoplasms / pathology*
  • Ovary / cytology
  • Propidium / chemistry
  • Propidium / metabolism
  • Semen / physiology*
  • Xenograft Model Antitumor Assays

Substances

  • Fluoresceins
  • Fluorescent Dyes
  • Propidium
  • Ethidium
  • Acridine Orange
  • diacetylfluorescein