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Carbon Monoxide Expedites Metabolic Exhaustion to Inhibit Tumor Growth

Wegiel, Barbara; Gallo, David; Csizmadia, Eva; Harris, Clair; Belcher, John; Vercellotti, Gregory M.; Penacho, Nuno; Seth, Pankaj; Sukhatme, Vikas and Ahmed, Asif, et al. (2013) In Cancer Research 73(23). p.7009-7021
Abstract
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... (More)
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. (C)2013 AACR. (Less)
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Cancer Research
volume
73
issue
23
pages
7009 - 7021
publisher
American Association for Cancer Research Inc.
external identifiers
  • wos:000328941200016
  • scopus:84890286026
ISSN
1538-7445
DOI
10.1158/0008-5472.CAN-13-1075
language
English
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yes
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80ab31c6-8ed8-4330-9993-4d369b48691b (old id 4330036)
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2014-03-03 07:56:19
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@article{80ab31c6-8ed8-4330-9993-4d369b48691b,
  abstract     = {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. (C)2013 AACR.},
  author       = {Wegiel, Barbara and Gallo, David and Csizmadia, Eva and Harris, Clair and Belcher, John and Vercellotti, Gregory M. and Penacho, Nuno and Seth, Pankaj and Sukhatme, Vikas and Ahmed, Asif and Pandolfi, Pier Paolo and Helczynski, Leszek and Bjartell, Anders and Persson, Jenny L and Otterbein, Leo E.},
  issn         = {1538-7445},
  language     = {eng},
  number       = {23},
  pages        = {7009--7021},
  publisher    = {American Association for Cancer Research Inc.},
  series       = {Cancer Research},
  title        = {Carbon Monoxide Expedites Metabolic Exhaustion to Inhibit Tumor Growth},
  url          = {http://dx.doi.org/10.1158/0008-5472.CAN-13-1075},
  volume       = {73},
  year         = {2013},
}