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Expert Opin Biol Ther. 2003 Apr;3(2):293-304.

BH3 domains as BCL-2 inhibitors: prototype cancer therapeutics.

Author information

1
Dana-Farber Cancer Institute, 1 Jimmy Fund Way, Boston, Massachusetts 02115, USA. anthony_letai@dfci.harvard.edu

Abstract

It is likely that most, if not all, cancer cells possess a mechanism for opposing programmed cell death, or apoptosis. One mechanism often used by cancer cells to escape apoptosis is the overexpression of B cell leukaemia/lymphoma-2 protein (BCL-2) or related antiapoptotic proteins. Inhibiting BCL-2, therefore, is an anticancer strategy worthy of attention. BCL-2 homology 3 (BH3) domains are alpha-helical segments found in BCL-2 family member proteins. In pro-apoptotic members, the BH3 domain is necessary for pro-apoptotic function. It has been shown that short peptides derived from the BH3 region possess intrinsic pro-death activity. Furthermore, certain peptides of this group exert their pro-death function by specifically binding BCL-2 and opposing BCL-2's antideath function. Therefore, BH3 domains are prototype BCL-2 inhibitors. Mimetics of BH3 domains, whether derived from peptides or small molecules, have promise as cancer therapeutics.

PMID:
12662143
DOI:
10.1517/14712598.3.2.293
[Indexed for MEDLINE]

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