INHIBITION OF HORMONE AND GROWTH-FACTOR RESPONSIVE AND RESISTANT HUMAN BREAST-CANCER CELLS BY CERES-18, A CELL REGULATORY SIALOGLYCOPEPTIDE

We have previously documented that CeReS-18, a cell regulatory sialogl ycopeptide, inhibits the cellular proliferation of normal and transfor med cell types from a diverse range of species. Most cell types studie s exhibit a similar sensitivity to the reversible but growth inhibitor y effects of CeReS-18 at 7 x 10(-8) M concentration, while at higher c oncentrations CeReS-18 can elicit cytotoxicity. The present study was conducted to examine the effect of CeReS-18 on the proliferation of hu man mammary epithelial carcinoma cells. MCF-7 cells, which are estroge n receptor positive (ER(+)), and BT-20 cells, which are estrogen recep tor negative (ER(-)), were utilized. Both cell lines show equal sensit ivity to growth inhibition elicited by CeReS-18. Complete cessation of cell cycling was achieved with 7 x 10(-8) M CeReS-18, and the arrest was shown to be completely reversible. Flow cytometric analysis, perfo rmed on CeReS-18 treated cells from both cell types, revealed that the majority of these cells were arrested in the G1 phase of the cell cyc le. When cells were treated simultaneously with inhibitor and stimulat ory concentrations of mitogens such as epidermal growth factor (EGF), basic fibroblast growth factor (b-FGF), estrogen, insulin-like growth factors I and II (IGFI and IGFII), no alteration of the inhibitory act ivity of CeReS-18 was observed. CeReS-18 clearly abrogated the mitogen ic activity that these growth factors elicited with human mammary carc inoma cells.