EasySep™小鼠TIL（CD45）正选试剂盒
产品号 #73592_C
表观遗传修饰剂；抑制组蛋白甲基转移酶SU(VAR)3-9
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总览
毛壳素（Chaetocin）是一种真菌毒素，最初由毛壳菌属（Chaetomium）产生，可抑制赖氨酸特异性组蛋白甲基转移酶（HMT）SU(VAR)3-9（IC₅₀=0.8 μM）。HMT负责组蛋白甲基化，从而影响异染色质化。毛壳素也能抑制G9a和DIM5（IC₅₀值分别为2.5 μM和3 μM；Cherblanc et al.; Greiner et al.）。毛壳素还能作为中枢氧化应激修复酶硫氧还蛋白还原酶-1（TrxR1；Km=4.6 μM）的竞争性底物和抑制剂，其作用比谷胱甘肽还原酶或硫氧还蛋白更有效（Tibodeau et al.）。
癌症研究
·诱导细胞氧化应激，选择性杀死癌细胞和快速增殖的原代细胞（Isham et al.; Spannhoff et al.）。
·减弱神经胶质瘤异种移植瘤的生长，同时伴随活性氧（ROS）产生的增加（Dixit et al.）。
细胞类型
癌细胞及细胞系
种属
人，小鼠，非人灵长类，其它细胞系，大鼠
研究领域
癌症
CAS 编号
28097-03-2
化学式
C₃₀H₂₈N₆O₆S₄
纯度
≥ 95 %
通路
表观遗传学
靶点
组蛋白甲基转移酶
产品说明书及文档
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相关材料与文献
文献 (6)
Chaetocin-induced ROS-mediated apoptosis involves ATM-YAP1 axis and JNK-dependent inhibition of glucose metabolism. Cell death & disease 2014 JAN
Abstract
Oxidative stress serves as an important regulator of both apoptosis and metabolic reprogramming in tumor cells. Chaetocin, a histone methyltransferase inhibitor, is known to induce ROS generation. As elevating basal ROS level sensitizes glioma cells to apoptosis, the ability of Chaetocin in regulating apoptotic and metabolic adaptive responses in glioma was investigated. Chaetocin induced glioma cell apoptosis in a ROS-dependent manner. Increased intracellular ROS induced (i) Yes-associated protein 1 (YAP1) expression independent of the canonical Hippo pathway as well as (ii) ATM and JNK activation. Increased interaction of YAP1 with p73 and p300 induced apoptosis in an ATM-dependent manner. Chaetocin induced JNK modulated several metabolic parameters like glucose uptake, lactate production, ATP generation, and activity of glycolytic enzymes hexokinase and pyruvate kinase. However, JNK had no effect on ATM or YAP1 expression. Coherent with the in vitro findings, Chaetocin reduced tumor burden in heterotypic xenograft glioma mouse model. Chaetocin-treated tumors exhibited heightened ROS, pATM, YAP1 and pJNK levels. Our study highlights the coordinated control of glioma cell proliferation and metabolism by ROS through (i) ATM-YAP1-driven apoptotic pathway and (ii) JNK-regulated metabolic adaptation. The elucidation of these newfound connections and the roles played by ROS to simultaneously shift metabolic program and induce apoptosis could provide insights toward the development of new anti-glioma strategies.
Chaetocin is a nonspecific inhibitor of histone lysine methyltransferases. Nature chemical biology 2013 MAR
Abstract
The anticancer agent chaetocin is a competitive substrate and inhibitor of thioredoxin reductase. Antioxidants & redox signaling 2009 MAY
Abstract
We recently reported that the antineoplastic thiodioxopiperazine natural product chaetocin potently induces cellular oxidative stress, thus selectively killing cancer cells. In pursuit of underlying molecular mechanisms, we now report that chaetocin is a competitive and selective substrate for the oxidative stress mitigation enzyme thioredoxin reductase-1 (TrxR1) with lower K(m) than the TrxR1 native substrate thioredoxin (Trx; chaetocin K(m) = 4.6 +/- 0.6 microM, Trx K(m) = 104.7 +/- 26 microM), thereby attenuating reduction of the critical downstream ROS remediation substrate Trx at achieved intracellular concentrations. Consistent with a role for TrxR1 targeting in the anticancer effects of chaetocin, overexpression of the TrxR1 downstream effector Trx in HeLa cells conferred resistance to chaetocin-induced, but not to doxorubicin-induced, cytotoxicity. As the TrxR/Trx pathway is of central importance in limiting cellular reactive oxygen species (ROS)--and as chaetocin exerts its selective anticancer effects via ROS imposition--the inhibition of TrxR1 by chaetocin has potential to explain its selective anticancer effects. These observations have important implications not just with regard to the mechanism of action and clinical development of chaetocin and related thiodioxopiperazines, but also with regard to the utility of molecular targets within the thioredoxin reductase/thioredoxin pathway in the development of novel candidate antineoplastic agents.
更多信息
| 种属 | Human, Mouse, Non-Human Primate, Other, Rat |
|---|---|
| Cas Number | 28097-03-2 |
| Chemical Formula | C₃₀H₂₈N₆O₆S₄ |
| 纯度 | ≥ 95% |
| Target | Histone Methyltransferase |
| Pathway | Epigenetic |
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