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, and 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.
Betz
N A
NA
Center for Basic Cancer Research, Division of Biology, Kansas State University, Manhattan 66506, USA.
Fattaey
H K
HK
Westhoff
B A
BA
Paulsen
A Q
AQ
Johnson
T C
TC
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000648:ultrastructure; D002118:Calcium / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D011960:Receptors, Estrogen / Q000502:physiology; D012795:Sialoglycoproteins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D011960:Receptors, Estrogen; D012795:Sialoglycoproteins; D002118:Calcium