TY - JOUR
T1 - Carbon monoxide expedites metabolic exhaustion to inhibit tumor growth
AU - Wegiel, Barbara
AU - Gallo, David
AU - Csizmadia, Eva
AU - Harris, Clair
AU - Belcher, John
AU - Vercellotti, Gregory M.
AU - Penacho, Nuno
AU - Seth, Pankaj
AU - Sukhatme, Vikas
AU - Ahmed, Asif
AU - Pandolfi, Pier Paolo
AU - Helczynski, Leszek
AU - Bjartell, Anders
AU - Persson, Jenny Liao
AU - Otterbein, Leo E.
N1 - 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]
PY - 2013/12
Y1 - 2013/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84890286026&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-13-1075
DO - 10.1158/0008-5472.CAN-13-1075
M3 - Article
C2 - 24121491
SN - 0008-5472
VL - 73
SP - 7009
EP - 7021
JO - Cancer Research
JF - Cancer Research
IS - 23
ER -