Inhibitory effects of dextran derivatives in vitro on the growth characteristics of premalignant and malignant human mammary epithelial cell lines.

The effects of two dextran derivatives (CMDBS-6 and CMDBS-12) on the growth rates of three human mammary epithelial cell lines (HBL100,HH9 and MCF7) were studied. CMDBS-6 markedly inhibited the growth of all lines, while CMDBS-12 and native dextran T40 had no effect on the growth of all lines. This inhibition was dose-dependent, reversible and inversely related to the concentration of fetal calf serum. The inhibitory effect of CMDBS-6 is cytostatic but not cytotoxic. Moreover, CMDBS-6 appears to have a stronger effect on HBL100 cells which are non-tumorigenic in nude mice. In contrast, the growth of HH9 cells, which are highly tumorigenic in nude mice, is less inhibited by CMDBS-6. Whereas CMDBS-6 inhibited the HBL100 cell anchorage, that of HH9 cells was not affected. By analysing the cell distribution in the various phases of the cell cycle, we have observed that CMDBS-6 arrested HBL100 and MCF7 cell mainly in the G0/GI phase. In contrast, HH9 cells were accumulated in the G2/M phase. When treated with CMDBS-6, human mammary cells slightly increased their granularities. These results demonstrate an antiproliferative activity of CMDBS-6 which could not be explained by an inactivation of mitogens provided by the serum but suggest that this compound could exert its cytostatic effects via a cell-specific mechanism.