CeReS-18, a novel cell surface sialoglycopeptide, induces cell cycle arrest and apoptosis in a calcium-sensitive manner

Very few growth inhibitors have been identified which can inhibit the proliferation of a broad spectrum of human breast cancer cell lines. CeReS-18, a novel cell surface sialoglycopeptide growth inhibitor, can reversibly inhibit the proliferation of both estrogen receptor positive (MCF-7) and negative (BT-20) human breast cancer cell lines. In addition, at concentrations above those required for the reversible inhibition of cell proliferation, CeReS-18 can also induce cell death in MCF-7 cells. Changes in nuclear and cytoplasmic morphology, characteristic of apoptosis, were detected in MCF-7 cells treated with a cytotoxic concentration of CeReS-18, and internucleosomal DNA cleavage was also observed. The sensitivity of MCF-7 and BT-20 cells to the biological properties of CeReS-18 could be influenced by altering the calcium concentration in the extracellular growth medium, such that when the calcium concentration in the environment was decreased, an increased sensitivity to CeReS-18-induced growth inhibition and cytotoxicity were observed. The addition of the calcium chelating agent EGTA to MCF-7 cells, cultured in a normal calcium environment, could mimic the increased sensitivity to the biological effects of CeReS-18 observed under reduced calcium conditions.