Antiangiogenic, antitumoural and antimetastatic effects of two distamycin A derivatives with anti-HIV-1 Tat activity in a Kaposi's sarcoma-like murine model |
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Authors: | Laura Possati Diana Campioni Francesco Sola Luciana Leone Luigi Ferrante Cecilia Trabanelli Marina Ciomei Marco Montesi Romina Rocchetti Simona Talevi Stefano Bompadre Antonella Caputo Giuseppe Barbanti-Brodano Alfredo Corallini |
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Affiliation: | (1) Institute of Biomedical Sciences, University of Ancona, Italy;(2) Department of Experimental and Diagnostic Medicine, Section of Microbiology, and Interdepartment Center for Biotechnology, University of Ferrara, Italy;(3) Pharmacia & Upjohn, Milano, Italy |
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Abstract: | 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. This revised version was published online in July 2006 with corrections to the Cover Date. |
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Keywords: | angiogenesis distamycin A derivatives HIV-1 Tat Kaposi’ s sarcoma metastasis |
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