期刊
CANCER RESEARCH
卷 70, 期 3, 页码 1101-1110出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-09-2889
关键词
-
类别
资金
- Agence Nationale de la Recherche [ANR-07-PCVI-0031-01]
- European Commission [LSHC-CT-2005-518417, HEALTH-F4-2007-200767]
- Region Alsace and the Association pour la Recherche sur le Cancer
- La Ligue Contre le Cancer
- Agence Nationale de la Recherche (ANR) [ANR-07-PCVI-0031] Funding Source: Agence Nationale de la Recherche (ANR)
Ongoing clinical trials are exploring anticancer approaches based on signaling by TRAIL, a ligand for the cell death receptors DR4 and DR5. In this study, we report on the selective apoptotic effects of multivalent DR5 binding peptides(TRAIL(mim/DR5)) on cancer cells in vitro and in vivo. Surface plasmon resonance revealed up to several thousand-fold increased affinities of TRAIL(mim/DR5)-receptor complexes on generation of divalent and trivalent molecules, the latter of which was achieved with a conformationally restricted adamantane core. Notably, only multivalent molecules triggered a substantial DR5-dependent apoptotic response in vitro. In tumor models derived from human embryonic kidney cells or primary foreskin fibroblasts, TRAIL(mim/DR5) peptides exerted a cancer cell-selective action that could synergize with resveratrol in a manner independent of p53. In a xenograft model of human colon cancer, a divalent TRAIL(mim/DR5) peptide inhibited tumor growth. Our results offer a proof-of-principle for the development of synthetic small molecules to trigger the TRAIL apoptosis pathway for cancer therapy. Cancer Res; 70(3); 1101-10. (C) 2010 AACR.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据