Tumor-selective killing by selenite in patient-matched pairs of normal and malignant prostate cells.

Abstract

BACKGROUND:

Selenium compounds have been shown to induce apoptosis in a variety of human prostate cancer cell lines. However, the effects of selenium have yet to be examined in normal and malignant cells derived from the same individual. Selenite metabolism consumes glutathione (GSH) and produces superoxide. The generation of reactive oxygen species is an important mechanism in selenite-induced apoptosis.

METHODS:

Three patient-matched pairs of primary prostatic epithelial cell cultures from normal and cancer were evaluated for their response to selenite. Apoptosis was measured and the differential response of normal and cancer cells was correlated with the expression of bcl-2, bax, GSH, and manganese superoxide dismutase (MnSOD).

RESULTS:

The cancer-derived cells were significantly more sensitive to selenite-induced apoptosis than the corresponding normal cells. Tumor-selective killing was not observed in cells treated with selenomethionine. The ratio of bcl-2:bax was decreased in the cancer-derived cells treated with selenite. Total GSH concentrations were similar in paired normal and cancer cells. Therefore, differences in GSH content do not appear to play a role in tumor-selective killing by selenite. Superoxide is a by-product of selenite metabolism and normal cells showed increased MnSOD expression and SOD activity compared to the cancer-derived cells. Prostate cancer cells treated with the MnSOD mimetic, MnTMPyP, were protected against the cytotoxic effects of selenite.

CONCLUSIONS:

Higher MnSOD expression in normal cells may play an important role in eliminating superoxide radicals produced as a result of selenite metabolism and contribute to the tumor-selective killing by selenite in prostate cancer.

• Authors: B Husbeck, L Nonn, D M Peehl, S J Knox
• Journal: The Prostate (Prostate) Vol. 66 Issue 2 Pg. 218-25 (Feb 01 2006) ISSN: 0270-4137 [Print] United States
• PMID: 16173037 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright 2005 Wiley-Liss, Inc.

Chemical References

• BAX protein, human
• Proto-Oncogene Proteins c-bcl-2
• bcl-2-Associated X Protein
• Superoxide Dismutase
• Glutathione
• Sodium Selenite

Topics

• Apoptosis (drug effects)
• Blotting, Western
• Cell Proliferation (drug effects)
• Cells, Cultured
• Epithelium (chemistry, drug effects)
• Glutathione (metabolism)
• Humans
• Immunohistochemistry
• Male
• Prostate (chemistry, cytology, drug effects, pathology)
• Prostatic Neoplasms (chemistry, pathology)
• Proto-Oncogene Proteins c-bcl-2 (analysis)
• Sensitivity and Specificity
• Sodium Selenite (metabolism, pharmacology)
• Superoxide Dismutase (metabolism)
• Tumor Cells, Cultured
• bcl-2-Associated X Protein (analysis)