Carbon monoxide expedites metabolic exhaustion to inhibit tumor growth

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 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. ©2013 AACR.

Publication DOI: https://doi.org/10.1158/0008-5472.CAN-13-1075
Divisions: College of Health & Life Sciences
College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
College of Health & Life Sciences > Aston Medical School
Additional Information: Funding: NIH [HL-071797, HL-076167]; AHA [10SDG2640091]; Julie Henry Fund at the Transplant Center of the BIDMC; British Heart Foundation [PG/06/114]; Medical Research Council [G0601295, G0700288]
Uncontrolled Keywords: Cancer Research,Oncology
Publication ISSN: 1538-7445
Full Text Link: http://cancerre ... tent/73/23/7009
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2013-12
Published Online Date: 2013-10-11
Authors: Wegiel, Barbara
Gallo, David
Csizmadia, Eva
Harris, Clair
Belcher, John
Vercellotti, Gregory M.
Penacho, Nuno
Seth, Pankaj
Sukhatme, Vikas
Ahmed, Asif (ORCID Profile 0000-0002-8755-8546)
Pandolfi, Pier Paolo
Helczynski, Leszek
Bjartell, Anders
Persson, Jenny Liao
Otterbein, Leo E.

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