Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Oncogene. 2008 Dec;27 Suppl 1:S149-57. doi: 10.1038/onc.2009.52.

Mimicking the BH3 domain to kill cancer cells.

Author information

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.

Abstract

Cancer cells show deviant behavior that induces apoptotic signaling. To survive, cancer cells typically acquire changes enabling evasion of death signals. One way they do this is by increasing the expression of anti-apoptotic BCL-2 proteins. Anti-apoptotic BCL-2 family proteins antagonize death signaling by forming heterodimers with pro-death proteins. Heterodimer formation occurs through binding of the pro-apoptotic protein's BH3 domain into the hydrophobic cleft of anti-apoptotic proteins. The BH3 mimetics are small molecule antagonists of the anti-apoptotic BCL-2 members that function as competitive inhibitors by binding to the hydrophobic cleft. Under certain conditions, antagonism of anti-apoptotic BCL-2 family proteins can unleash pro-death molecules in cancer cells. Thus, the BH3 mimetics are a new class of cancer drugs that specifically target a mechanism of cancer cell survival to selectively kill cancer cells.

PMID:
19641500
[PubMed - indexed for MEDLINE]
PMCID:
PMC3733265
Free PMC Article

Publication Types, MeSH Terms, Substances, Grant Support

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Write to the Help Desk