Just found this today. Didn't see it posted here, and wanted any of
you who haven't seen it to know about it.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=11857423&dopt=Abstract

Int J Cancer. 2002 Mar 10;98(2):297-309.
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Inhibition of cell proliferation, invasion, tumor growth and
metastasis by an oral non-antimicrobial tetracycline analog (COL-3)
in a metastatic prostate cancer model.
Lokeshwar BL, Selzer MG, Zhu BQ, Block NL, Golub LM.

Sylvester Comprehensive Cancer Center and Department of Urology,
University of Miami School of Medicine, Miami, FL 33101, USA.
BLOKESHW@...

Antibiotic forms of tetracycline exhibit antitumor activity in some
tumor models. However, their low in vivo efficacy and associated
morbidity limit their long-term application in cancer therapy. This
report appraises the efficacy of doxycycline (DC) and non-
antimicrobial, chemically modified tetracyclines (CMTs) against
prostate cancer. Both DC and several CMTs inhibited prostate tumor
cell proliferation in vitro. Some of the CMTs were significantly
more potent than DC. One of the CMTs, 6-deoxy, 6-demethyl, 4-de-
dimethylamino tetracycline (CMT-3, COL-3), was the most potent
inhibitor (50% inhibition dose [GI(50)] < or = 5.0 ,microg/ml).

Exposure of tumor cells to CMT-3 induced both apoptosis and
necrosis. Mitochondrial depolarization and increased levels of
reactive hydroxyl radicals were also observed in cells treated with
CMT-3. Cell cycle arrest at the G(0)/G(1) compartment was observed
in CMT-3- and DC-treated cells. DC and CMTs also inhibited the
invasive potential of the tumor cells in vitro, from 10% (CMT-6) to
>90% (CMT-3). CMT-3 and DC decreased matrix metalloproteinase (MMP)-
2, tissue inhibitor of MMP (TIMP)-1 and TIMP-2 secretion in treated
cultures and inhibited activity of secreted MMPs, CMT-3 was a
stronger inhibitor. Daily oral gavage of DC and CMT-3 inhibited
tumor growth and metastasis in the Dunning MAT LyLu rat prostate
tumor. Decreases in tumor growth (27-35%) and lung metastases were
observed (28.9 +/- 15.4 sites/animal [CMT-3-treated] versus 43.6 +/-
18.8 sites/animal [DC-treated] versus 59.5 +/- 13.9 [control]; p <
0.01]. A delay in tumor growth (27 +/- 9.3%, p < 0.05), reduction in
metastases (58 +/- 8%) and decrease in tumor incidences (55 +/- 9%,
CMT-3-treated) were also observed, when rats were predosed for 7
days. No significant drug-induced morbidity was observed in any of
the animals. These results, along with a recently concluded clinical
trial, suggest a potential use of CMT-3 as an oral, nontoxic drug to
treat metastatic prostate and other cancers. Copyright 2001 Wiley-
Liss, Inc.

PMID: 11857423 [PubMed - indexed for MEDLINE]