Suppression of cancer cachexia by 20S,21-epoxy-resibufogenin-3-acetate -: a novel nonpeptide IL-6 receptor antagonist

被引：47

作者：

Enomoto, A

Rho, MC

Fukami, A

Hiraku, O

Komiyama, K

Hayashi, M

机构：

[1] Kitasato Inst, Minato Ku, Tokyo 1088642, Japan

[2] Fanel Co Ltd, Cent Res Lab, Totsuka Ku, Yokohama, Kanagawa 2440806, Japan

[3] Korea Res Inst Biosci & Biotechnol, Taejon 305333, South Korea

[4] Kitasato Univ, Minato Ku, Tokyo 1088642, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2004年 / 323卷 / 03期

关键词：

IL-6; cancer cachexia; epoxy-resibufogenin; receptor antagonist; 5 ' DFUR;

D O I：

10.1016/j.bbrc.2004.08.196

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

While screening for novel IL-6 inhibitors, we synthesized 20S, 21-epoxy-resibufogenin-3-acetate (ERBA). ERBA dose-dependently suppressed IL-6-induced cell growth with an IC50 value of 5.3 muM and caused a parallel rightward shift of dose-response curves to IL-6. Analysis of data yields a pA2 of 5.83 and a slope of 0.99. ERBA did not affect IL-2-, IL-3-, and GCSF-dependent cell growth, or tumor necrosis factor alpha-induced growth suppression, nor did ERBA affect osteoclast formation induced by IL-11, leukemia inhibitory factor, and 1alpha,25-dihydroxyvitamin D-3. Receptor assay showed that ERBA dose-dependently suppressed IL-6 binding to IL-6 receptor (IL-6R). Furthermore, no band existing at the position of IL-6R in Western blots of ERBA-treated cells when stimulated with IL-6:ERBA suppresses IL-6 activity by blocking the binding of IL-6 to IL-6R. In an experimental model of colon 26-induced cancer cachexia, ERBA markedly inhibited body weight loss. ERBA is a specific small molecule with IL-6R-antagonist activity. (C) 2004 Published by Elsevier Inc.

引用

页码：1096 / 1102

页数：7

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