Carbon Monoxide Expedites Metabolic Exhaustion to Inhibit Tumor Growth
(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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https://lup.lub.lu.se/record/4330036
- author
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Cancer Research
- volume
- 73
- issue
- 23
- pages
- 7009 - 7021
- publisher
- American Association for Cancer Research Inc.
- external identifiers
-
- wos:000328941200016
- scopus:84890286026
- pmid:24121491
- ISSN
- 1538-7445
- DOI
- 10.1158/0008-5472.CAN-13-1075
- language
- English
- LU publication?
- yes
- id
- 80ab31c6-8ed8-4330-9993-4d369b48691b (old id 4330036)
- date added to LUP
- 2016-04-01 13:29:11
- date last changed
- 2022-05-15 05:23:55
@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}}, doi = {{10.1158/0008-5472.CAN-13-1075}}, volume = {{73}}, year = {{2013}}, }