The tetracycline analogs minocycline and doxycycline inhibit angiogenesis in vitro by a non-metalloproteinase-dependent mechanism

Cancer Chemotherapy and Pharmacology
S Gilbertson-BeadlingR Poorman

Abstract

The tetracycline analogs minocycline and doxycycline are inhibitors of metalloproteinases (MMPs) and have been shown to inhibit angiogenesis in vivo. To further study the mechanism of action of these compounds we tested them in an in vitro model of angiogenesis: aortic sprouting in fibrin gels. Angiogenesis was quantitated in this system by a unique application of planar morphometry. Both compounds were found to potently inhibit angiogenesis in this model. To further characterize the activity of these compounds against MMPs, we determined the IC50S of both compounds against representatives of three classes of metalloproteinases: fibroblast collagenase, stromelysin, and gelatinase A. Doxycycline was found to inhibit collagenase, gelatinase A and stromelysin with IC50S of 452 microM, 56 microM and 32 microM, respectively. Minocycline was found to inhibit only stromelysin in the micromolar range with an IC50 of 290 microM. Since these results suggest that these compounds may not have been inhibiting in vitro angiogenesis by an MMP-dependent mechanism, we decided to test the effects of the potent MMP inhibitor BB-94. This compound failed to inhibit aortic sprouting in fibrin gels, thus strongly suggesting that both doxycycline and ...Continue Reading

References

Nov 1, 1979·Analytical Biochemistry·T E Cawston, A J Barrett
Jan 1, 1992·Antimicrobial Agents and Chemotherapy·K SuomalainenY T Konttinen
Oct 30, 1992·Biochemical and Biophysical Research Communications·C GuerinH Brem
Jan 1, 1992·Cancer Chemotherapy and Pharmacology·E A SotomayorE Frei
Dec 1, 1990·Cancer Metastasis Reviews·W G Stetler-Stevenson
Apr 1, 1990·Trends in Genetics : TIG·L M Matrisian
Oct 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·R MontesanoL Orci
Oct 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·S M WilhelmG I Goldberg
Apr 1, 1994·Developmental Biology·C FisherM A Mitchell

❮ Previous
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Citations

Feb 24, 2005·Cancer Chemotherapy and Pharmacology·Mary RichardsonGurmit Singh
Jan 15, 2014·Archives of Biochemistry and Biophysics·Hui-Jung JungWon-Ki Baek
Jan 7, 2004·Journal of the Neurological Sciences·Shauna KirkStephen Karlik
Mar 14, 2002·The American Journal of Pathology·Michelle P BendeckStephanie M Farwell
Aug 6, 2003·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Tejinder S Ahuja
Jan 29, 2002·Toxicology in Vitro : an International Journal Published in Association with BIBRA·H Babich, D A Tipton
Feb 7, 2001·Journal of the National Cancer Institute·M Hidalgo, S G Eckhardt
Feb 19, 2002·Antimicrobial Agents and Chemotherapy·Katrina L MealeyDeborah T Kochevar
Apr 13, 2007·American Journal of Nephrology·Afsoon Emami NainiAli Amiran
Nov 4, 2008·Biological Chemistry·Cary W EsselensJoaquín Arribas
Dec 17, 2011·Journal of the American Veterinary Medical Association·Dean J Cerf, Eric C Lindquist
Aug 1, 2013·Indian Journal of Pharmaceutical Sciences·R R Somani, U V Bhanushali
Oct 22, 2013·Archives of Virology·Hussin A RothanRohana Yusof
Jul 14, 2012·Expert Review of Respiratory Medicine·Angelo M Taveira-DaSilva, Joel Moss
Jul 2, 2005·Expert Opinion on Emerging Drugs·K J O'Byrne, W P Steward
Feb 9, 2016·Expert Opinion on Drug Metabolism & Toxicology·Jia-Sin YangShun-Fa Yang
Aug 24, 2013·Current Eye Research·Vesna Jovanovic, Ljubisa Nikolic
Oct 23, 2012·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·N Garrido-MesaJ Gálvez
Feb 4, 2010·Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics·Nestor CohencaLea Assed Bezerra da Silva
Aug 4, 2015·The British Journal of Radiology·Gian L NataliMassimo Rollo
Sep 3, 2003·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Patricia A HebdaAlan Wells
Nov 30, 2006·International Journal of Cancer. Journal International Du Cancer·Petros X E MouratidisAngus G Dalgleish
Jan 9, 2009·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Wouter HuvenneClaus Bachert
Jul 31, 2008·Chembiochem : a European Journal of Chemical Biology·Faith E JacobsenSeth M Cohen
Aug 6, 2013·Journal of Esthetic and Restorative Dentistry : Official Publication of the American Academy of Esthetic Dentistry ... [et Al.]·Jorge PerdigãoAlessandro D Loguercio
Aug 7, 2004·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Milin R AcharyaAlex Sparreboom
Jul 1, 1997·Research in Veterinary Science·M W OrthT M Schmid
Jan 7, 2003·Hematology/oncology Clinics of North America·W Thomas PurcellManuel Hidalgo
Jul 25, 2015·Biological Research·Jung Mi YoonChan Gil Kim
May 26, 2015·Translational Stroke Research·Sahar SolimanSusan C Fagan
Mar 20, 2010·Journal of the American College of Cardiology·Satoru OhshimaJagat Narula
Jul 22, 2010·Respiratory Medicine·Connie G GlasgowJoel Moss
Sep 26, 2003·The American Journal of Pathology·Muzharul M IslamMichelle P Bendeck

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