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 journalArticle

118 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)7009-7021
Number of pages13
JournalCancer Research
Volume73
Issue number23
DOIs
StatePublished - Dec 1 2013

Fingerprint

Carbon Monoxide
Heme Oxygenase-1
Growth
Neoplasms
Prostatic Neoplasms
Oxygen Consumption
Energy Metabolism
Free Radicals
Mitochondria
Carcinogenesis
Apoptosis
Phenotype
Drug Therapy

Cite this

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; Ahmed, Asif; Pandolfi, Pier Paolo; Helczynski, Leszek; Bjartell, Anders; Persson, Jenny Liao; Otterbein, Leo E.

In: Cancer Research, Vol. 73, No. 23, 01.12.2013, p. 7009-7021.

Research output: Contribution to journalArticle

Wegiel, B, Gallo, D, Csizmadia, E, Harris, C, Belcher, J, Vercellotti, GM, Penacho, N, Seth, P, Sukhatme, V, Ahmed, A, Pandolfi, PP, Helczynski, L, Bjartell, A, Persson, JL & Otterbein, LE 2013, 'Carbon monoxide expedites metabolic exhaustion to inhibit tumor growth', Cancer Research, vol. 73, no. 23, pp. 7009-7021. https://doi.org/10.1158/0008-5472.CAN-13-1075
Wegiel, Barbara ; Gallo, David ; Csizmadia, Eva ; Harris, Clair ; Belcher, John ; Vercellotti, Gregory M. ; Penacho, Nuno ; Seth, Pankaj ; Sukhatme, Vikas ; Ahmed, Asif ; Pandolfi, Pier Paolo ; Helczynski, Leszek ; Bjartell, Anders ; Persson, Jenny Liao ; Otterbein, Leo E. / Carbon monoxide expedites metabolic exhaustion to inhibit tumor growth. In: Cancer Research. 2013 ; Vol. 73, No. 23. pp. 7009-7021.
@article{d13dff1bd74a42bfaa9e067977f3009b,
title = "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.",
author = "Barbara Wegiel and David Gallo and Eva Csizmadia and Clair Harris and John Belcher and Vercellotti, {Gregory M.} and Nuno Penacho and Pankaj Seth and Vikas Sukhatme and Asif Ahmed and Pandolfi, {Pier Paolo} and Leszek Helczynski and Anders Bjartell and Persson, {Jenny Liao} and Otterbein, {Leo E.}",
year = "2013",
month = "12",
day = "1",
doi = "10.1158/0008-5472.CAN-13-1075",
language = "English (US)",
volume = "73",
pages = "7009--7021",
journal = "Cancer Research",
issn = "0008-5472",
number = "23",

}

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.

PY - 2013/12/1

Y1 - 2013/12/1

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.

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.

UR - http://www.scopus.com/inward/record.url?scp=84890286026&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84890286026&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-13-1075

DO - 10.1158/0008-5472.CAN-13-1075

M3 - Article

VL - 73

SP - 7009

EP - 7021

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 23

ER -