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

Rose Fife, G. W. Sledge, C. Proctor, J. Dunn

Research output: Contribution to journalArticle

1 Citation (Scopus)

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
JournalJournal of Investigative Medicine
Volume44
Issue number3
StatePublished - 1996

Fingerprint

Doxycycline
Matrix Metalloproteinases
Prostatic Neoplasms
Cells
Apoptosis
Cell Proliferation
Cell proliferation
Tumors
Breast Neoplasms
DNA
DNA Fragmentation
Cell death
Osteosarcoma
Gelatin
Cell culture
Nude Mice
Lung Neoplasms
Neoplasms
Cell Death
Neoplasm Metastasis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Doxycycline inhibits matrix metalloproteinase activity and enhances apoptosis in human prostate cancer cells. / Fife, Rose; Sledge, G. W.; Proctor, C.; Dunn, J.

In: Journal of Investigative Medicine, Vol. 44, No. 3, 1996.

Research output: Contribution to journalArticle

@article{6b14a02125c744ad8d3e0d27898ee8a1,
title = "Doxycycline inhibits matrix metalloproteinase activity and enhances apoptosis in human prostate cancer cells",
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.",
author = "Rose Fife and Sledge, {G. W.} and C. Proctor and J. Dunn",
year = "1996",
language = "English",
volume = "44",
journal = "Journal of Investigative Medicine",
issn = "1081-5589",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - Doxycycline inhibits matrix metalloproteinase activity and enhances apoptosis in human prostate cancer cells

AU - Fife, Rose

AU - Sledge, G. W.

AU - Proctor, C.

AU - Dunn, J.

PY - 1996

Y1 - 1996

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0005943942&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0005943942&partnerID=8YFLogxK

M3 - Article

VL - 44

JO - Journal of Investigative Medicine

JF - Journal of Investigative Medicine

SN - 1081-5589

IS - 3

ER -