THE TETRAPEPTIDE ACSDKP, A PHYSIOLOGICAL INHIBITOR OF NORMAL-CELL PROLIFERATION, REDUCES THE S-PHASE ENTRY OF CONTINUOUS CELL-LINES

The tetrapeptide AcSer-Asp-Lys-Pro (AcSDKP), a physiological negative regulator of cell proliferation, inhibits the progression of normal qu iescent cells to the S phase of the cycle, while it is inactive in the proliferation of permanent cell lines and of freshly isolated leukemi c cells. It protects normal hematopoietic stem cells and progenitors f rom the toxic effects of anticancer drugs, We studied the effects of A cSDKP on the S phase entry of mouse and chicken continuous cell lines MS-K, 3T3, MDCC-PA9, and RIIDCC-MSB1 that were previously partially sy nchronized by culture under conditions oflow serum concentrations or s erum starvation. Our results demonstrate that AcSDKP reduces the proli feration of these cell lines when they are cultured under these define d conditions. They show that AcSDKP acts on cells of continuous cell l ines as it does on hepatocytes or hematopoietic cells in vivo or on fr eshly isolated cells in vitro, by blocking or retarding their entry in to S phase from early G(1). (C) 1996 Academic Press, Inc.