Carbon monoxide expedites metabolic exhaustion to inhibit tumor growth.
Carbon monoxide expedites metabolic exhaustion to inhibit tumor growth.
复制标题
一氧化碳加快了代谢衰竭以抑制肿瘤的生长。
DOI：
10.1158/0008-5472.can-13-1075
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发表时间：
2013-12-01
期刊：
影响因子：
11.2
通讯作者：
Otterbein LE
中科院分区：
文献类型：
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作者：
Wegiel B;Gallo D;Csizmadia E;Harris C;Belcher J;Vercellotti GM;Penacho N;Seth P;Sukhatme V;Ahmed A;Pandolfi PP;Helczynski L;Bjartell A;Persson JL;Otterbein LE
癌细胞的一个典型特征是它们代谢获得高度糖酵解表型。一氧化碳（CO）是癌细胞中细胞保护分子血红素加氧酶-1（HO-1）的产物之一，与癌的发生和治疗耐药性有关。然而，CO和HO-1对这些过程的功能贡献很难定义。在人类前列腺癌中，我们发现HO-1位于恶性细胞的核中，在中等分化的肿瘤中具有低酶活性，与相对较差的临床结果相关。暴露于CO敏感的前列腺癌细胞，但不是正常细胞化疗，生长停滞和凋亡诱导体内部分通过有丝分裂灾难。CO靶向癌细胞中的线粒体活性，如通过更高的氧消耗、自由基产生和线粒体崩溃所证明的。总的来说，我们的研究结果表明，一氧化碳通过快速刺激癌细胞生物能量学，最终导致代谢衰竭，从而瞬时诱导抗Warburg效应。
One classical feature of cancer cells is their metabolic acquisition of a highly glycolytic phenotype. Carbon monoxide (CO), one of the products of the cytoprotective molecule heme oxygenase-1 (HO-1) in cancer cells, has been implicated in carcinogenesis and therapeutic resistance. However, the functional contributions of CO and HO-1 to these processes are poorly defined. In human prostate cancers, we found that HO-1 was nuclear localized in malignant cells, with low enzymatic activity in moderately differentiated tumors correlating with relatively worse clinical outcomes. Exposure to CO sensitized prostate cancer cells but not normal cells to chemotherapy, with growth arrest and apoptosis induced in vivo in part through mitotic catastrophe. CO targeted mitochondria activity in cancer cells as evidenced by higher oxygen consumption, free radical generation and mitochondrial collapse. Collectively, our findings indicated that CO transiently induces an anti-Warburg effect by rapidly fueling cancer cell bioenergetics, ultimately resulting in metabolic exhaustion.