IN-VITRO MODULATION OF DOXORUBICIN AND DOCETAXEL ANTITUMORAL ACTIVITYBY METHYL-BETA-CYCLODEXTRIN

Methyl-beta-cyclodextrin (MEBCD) was investigated for its effect on th e antitumoral activity of various antineoplastic agents (doxorubicin ( DOX), docetaxel (DXL), 5-fluorouracil (5-FU) and cisplatin (CDDP)) in three different human parental sensitive cancer cell lines (K562 S, MC F7 S and A2780 S) and their multidrug resistant variant sublines (K562 R, MCF7 R and A2780 R). At non-cytotoxic concentrations, MEBCD was ab le to increase significantly DOX and DXL cytotoxic activity in all the cell lines tested. The sensitisation ratios (IC50 drug control/IC50 d rug-MEBCD treated) ranged from 3.1 to 14.3. Moreover, intracellular DO X accumulation, determined by high-performance liquid chromatography, was also increased when cells were treated with MEBCD combined with DO X (approximately 2-3-fold). The effects of MEBCD in resistant sublines were greater than in their parental sensitive cell lines. Other exper iments demonstrated that the action of the MEBCD was independent of DO X. These data provided a basis for the potential therapeutic applicati on of MEBCD in cancer therapy. (C) 1998 Elsevier Science Ltd.