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 sialoglycopeptide, inhibits the cellular proliferation of normal and transformed cell types from a diverse range of species. Most cell types studies exhibit a similar sensitivity to the reversible but growth inhibitory effects of CeReS-18 at 7 x 10(-8) M concentration, while at higher concentrations CeReS-18 can elicit cytotoxicity. The present study was conducted to examine the effect of CeReS-18 on the proliferation of human mammary epithelial carcinoma cells. MCF-7 cells, which are estrogen receptor positive (ER(+)), and BT-20 cells, which are estrogen receptor negative (ER(-)), were utilized. Both cell lines show equal sensitivity 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, performed 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 cycle. When cells were treated simultaneously with inhibitor and stimulatory 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 activity of CeReS-18 was observed. CeReS-18 clearly abrogated the mitogenic activity that these growth factors elicited with human mammary carcinoma cells.