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Induction of wild‐type p53, Bax, and acidic endonuclease during somatostatin‐signaled apoptosis in MCF‐7 human breast cancer cells
Author(s) -
Sharma Kamal,
Srikant Coimbatore B.
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980413)76:2<259::aid-ijc14>3.0.co;2-7
Subject(s) - apoptosis , cancer research , cytotoxic t cell , somatostatin , dna fragmentation , programmed cell death , biology , cell growth , cell culture , cell cycle checkpoint , growth inhibition , cancer cell , mcf 7 , fragmentation (computing) , cancer , cell cycle , medicine , endocrinology , biochemistry , in vitro , human breast , genetics , ecology
Somatostatin (SST) analogs inhibit tumor cell growth by exerting direct anti‐proliferative effects with cytostatic (growth arrest) or cytotoxic (apoptosis) consequences. The SST analog SMS 201‐995 (octreotide, OCT) inhibits growth of MCF‐7 human breast adenocarcinoma cells, which express multiple SSTRs. Its action has been reported to result in either apoptosis or growth arrest, but the underlying mechanisms have not been elucidated in this tumor cell model. Here, we report that OCT elicits cytotoxic response in these cells, leading to apoptosis, which is associated with a rapid, time‐dependent induction of wild‐type p53 and an increase in Bax. There was no G 1 cell‐cycle arrest in these cells during OCT treatment as suggested by the decrease in G 1 /S ratio and the lack of induction of pRb and p21. Additionally, we demonstrate that OCT‐induced DNA fragmentation in this cell line is due to selective activation of a cation‐insensitive acidic endonuclease. Our data provide a rationale for utilizing SST analogs to treat SSTR‐positive breast cancer cells expressing wild‐type p53. Int. J. Cancer 76:259–266, 1998.© 1998 Wiley‐Liss, Inc.