CELL-CYCLE DEPENDENT INDUCTION OF APOPTOSIS BY SOMATOSTATIN ANALOG SMS-201-995 IN ATT-20 MOUSE PITUITARY-CELLS

Somatostatin (SS) and its analogs exert direct antiproliferative effects in a variety of tumor cells not only by inhibiting the mitogenic signalling of growth factor receptor kinases, but also by inducing apoptosis. In this study, the apoptotic effect of the octreotide SS analog, SMS 201-995, was investigated in phase synchronized AtT-20 mouse pituitary tumor cells. SMS 201-995 added to cells synchronized in G(1) or in G(2) phases induces apoptosis which is manifested in the subsequent cell cycle. No evidence of apoptosis was seen in cells subjected to cell cycle arrest in G(1) by lovastatin or in G(2) with 160 nM staurosporine. SMS 201-995 did not induce detectable apoptosis in unsynchronized cells which remained predominantly in G(1) phase. These findings provide the first documentation that SS peptides regulate cell growth in G(2) to induce apoptosis. (C) 1995 Academic Press, Inc.