Carbon monoxide expedites metabolic exhaustion to inhibit tumor growth

Barbara Wegiel, David Gallo, Eva Csizmadia, Clair Harris, John Belcher, Gregory M. Vercellotti, Nuno Penacho, Pankaj Seth, Vikas Sukhatme, Asif Ahmed, Pier Paolo Pandolfi, Leszek Helczynski, Anders Bjartell, Jenny Liao Persson, Leo E. Otterbein

Research output: Contribution to journalArticlepeer-review

307 Scopus citations


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 throughmitotic 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.

Original languageEnglish (US)
Pages (from-to)7009-7021
Number of pages13
JournalCancer Research
Issue number23
StatePublished - Dec 1 2013


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