Doxycycline inhibits matrix metalloproteinase activity and enhances apoptosis in human prostate cancer cells

R. S. Fife, G. W. Sledge, C. Proctor, J. Dunn

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Abstract

The malrix melalloproteinases (MMPs) are a family of enzymes that play a key rule in the invasion, metastasis, and angiogenesis of many tumors, including prostate cancer. We have a longstanding interest in agents that have activity as MMP inhibitors as potential antltumor drugs. We previously demonstrated that one such agent, doxycycline (dox), a synthetic letracycline, inhibits MMPs and cell proliferation in human breast cancer cells, osteosarcoma cells, and lung cancer cells. We also have demonstrated that in an in vivo model of metastatic breast cancer in athymic mice dox inhibits tumor size and regrowth after resection. In the present study, we incubated the LNCaP human prostate cancer cell line with 10 Mg/rnl of dox and found that MMPs were suppressed by 50-75%, as determined by gelatin zymography, compared to untreated cultures. Probably more significantly, cell death occurred by 4 days after exposure to dox, while cell proliferation was normal in untreated cells. Proliferation of cells incubated with 5 g/ml of dox was suppressed approximately 6-fold. Furthermore, DNA fragmentation consistent with apoptosis was demonstrated by DNA laddering in treated cells (10 fjg/ml of dox). These data suggest that dox, and possibly other MMP inhibitors, might have a therapeutic role in the management of prostate cancer. We are in the process of examining this possibility in an alhymic mouse model.

Original languageEnglish (US)
Pages (from-to)249a
JournalJournal of Investigative Medicine
Volume44
Issue number3
StatePublished - Jan 1 1996

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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