minocycline and Sarcoma--Kaposi

Tetracyclines are broad-spectrum antibiotics that act as such at the ribosomal level where they interfere with protein synthesis. They were first widely prescribed by dermatologists in the early 1950s when it was discovered that they were effective as a treatment for acne. More recently, biologic actions affecting inflammation, proteolysis, angiogenesis, apoptosis, metal chelation, ionophoresis, and bone metabolism have been researched. The therapeutic effects of tetracycline and its analogues in various diseases have also been investigated. These include rosacea, bullous dermatoses, neutrophilic diseases, pyoderma gangrenosum, sarcoidosis, aortic aneurysms, cancer metastasis, periodontitis, and autoimmune disorders such as rheumatoid arthritis and scleroderma. We review the nonantibiotic properties of tetracycline and its analogues and their potential for clinical application.

Topics: Acne Vulgaris; Anti-Bacterial Agents; Anti-Inflammatory Agents; Aortic Aneurysm, Abdominal; Apoptosis; Arthritis, Rheumatoid; Doxycycline; Humans; Matrix Metalloproteinases; Minocycline; Neoplasms; Neovascularization, Physiologic; Periodontitis; Rosacea; Sarcoma, Kaposi; Skin Diseases; Skin Diseases, Vesiculobullous; Tetracyclines

The antiangiogenic, antitumoural and antimetastatic effects of two novel sulphonic derivatives of distamycin A, PNU145156E and PNU153429, were studied in a Kaposi's sarcoma-like tumour model obtained by injecting nude mice with cells releasing extracellular HIV-Tat protein, derived from a tumour which developed in a BK virus/tat transgenic mouse. Both PNU145156E and PNU153429 were administered intraperitoneally every fourth day for three weeks at doses of 100 or 50 mg/kg of body weight respectively, starting one day after injecting the tumour cells. Both drugs delayed tumour growth in nude mice, preventing neovascularization induced by the Tat protein. PNU153429 also significantly reduced the number and size of spontaneous tumour metastases. Both effects on tumour growth and metastases were augmented by treating simultaneously nude mice with 7.5 mg/kg of body weight of minocycline given per os daily for four weeks starting four days after injecting the tumour cells. Neither acute nor chronic toxic side-effects were observed during the life span of treated nude mice. Due to their antiangiogenic and anti-Tat effects, these drugs are promising for the treatment of Kaposi's sarcoma in AIDS patients.

Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Distamycins; Drug Screening Assays, Antitumor; Female; Gene Products, tat; Genes, tat; HIV-1; Male; Mice; Mice, Nude; Mice, Transgenic; Minocycline; Neoplasm Metastasis; Neoplasm Proteins; Neoplasm Transplantation; Neovascularization, Pathologic; Sarcoma, Kaposi; tat Gene Products, Human Immunodeficiency Virus; Transfection