ANTIPROLIFERATIVE EFFECT OF METHYL-BETA-CYCLODEXTRIN IN-VITRO AND IN HUMAN TUMOR XENOGRAFTED ATHYMIC NUDE-MICE

The anti-tumour activity of methyl-beta-cyclodextrin (MEBCD), a cyclic oligosaccharide known for its interaction with the plasma membrane, w as investigated in vitro and in vivo and compared with that of doxorub icin (DOX) in the human tumour models MCF7 breast carcinoma and A2780 ovarian carcinoma. In vitro proliferation was assessed using the MTT a ssay. In vivo studies were carried out using xenografted Swiss nude mi ce injected weekly i.p. with MEBCD at 300 or 800 mg kg(-1) or DOX at 2 mg kg(-1), during 2 months. Under these conditions, MEBCD was active against MCF7 and A2780 cell lines and tumour xenografts. For each tumo ur model, the tumoral volume of the xenografted mice treated with MEBC D was at least twofold reduced compared with the control group. In the MCF7 model, MEBCD (800 mg kg(-1)) was more active than DOX (2 mg kg(- 1)). After 56 days of treatment with MEBCD, no toxicologically meaning ful differences were observed in macroscopic and microscopic parameter s compared with controls. The accumulation of MEBCD in normal and tumo ur tissues was also assessed using a chromatographic method. Results i ndicated that after a single injection of MEBCD, tumour, liver and kid neys accumulated the highest concentrations of MEBGD. These results pr ovided a basis for the potential therapeutic application of MEBCD in c ancer therapy.