Antiangiogenic, antitumoural and antimetastatic effects of two distamycin A derivatives with anti-HIV-1 Tat activity in a Kaposi's sarcoma-like murine model

The antiangiogenic, antitumoural and antimetastatic effects of two novel su lphonic derivatives of distamycin A, PNU145156E and PNU153429, were studied in a Kaposi's sarcoma-like tumour model obtained by injecting nude mice wi th cells releasing extracellular HIV-Tat protein, derived from a tumour whi ch developed in a BK virus/tat transgenic mouse. Both PNU145156E and PNU153 429 were administered intraperitoneally every fourth day for three weeks at doses of 100 or 50 mg/kg of body weight respectively, starting one day aft er injecting the tumour cells. Both drugs delayed tumour growth in nude mic e, 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 s imultaneously 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 c ells. Neither acute nor chronic toxic side-effects were observed during the life span of treated nude mice. Due to their antiangiogenic and anti-Tat e ffects, these drugs are promising for the treatment of Kaposi's sarcoma in AIDS patients.