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Dig Liver Dis. 2014 Apr;46(4):369-75. doi: 10.1016/j.dld.2013.12.007. Epub 2014 Jan 14.

Antiproliferative effects of carbon monoxide on pancreatic cancer.

Author information

1
Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, Prague 2, Czech Republic; 4th Department of Internal Medicine, 1st Faculty of Medicine, Charles University in Prague, Prague 2, Czech Republic. Electronic address: vitek@cesnet.cz.
2
Department of Biochemistry and Microbiology, Institute of Chemical Technology, Prague 6, Czech Republic.
3
Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, Prague 2, Czech Republic.
4
Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK; School of Life & Health Sciences, Aston University, Birmingham, UK.
5
Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
6
Department of Biochemistry and Microbiology, Institute of Chemical Technology, Prague 6, Czech Republic. Electronic address: Tomas.Ruml@vscht.cz.

Abstract

BACKGROUND:

Carbon monoxide, the gaseous product of heme oxygenase, is a signalling molecule with a broad spectrum of biological activities. The aim of this study was to investigate the effects of carbon monoxide on proliferation of human pancreatic cancer.

METHODS:

In vitro studies were performed on human pancreatic cancer cells (CAPAN-2, BxPc3, and PaTu-8902) treated with a carbon monoxide-releasing molecule or its inactive counterpart, or exposed to carbon monoxide gas (500 ppm/24h). For in vivo studies, pancreatic cancer cells (CAPAN-2/PaTu-8902) were xenotransplanted subcutaneously into athymic mice, subsequently treated with carbon monoxide-releasing molecule (35 mg/kg b.w. i.p./day), or exposed to safe doses of carbon monoxide (500 ppm 1h/day; n = 6 in each group).

RESULTS:

Both carbon monoxide-releasing molecule and carbon monoxide exposure significantly inhibited proliferation of human pancreatic cancer cells (p<0.05). A substantial decrease in Akt phosphorylation was observed in carbon monoxide-releasing molecule compared with inactive carbon monoxide-releasing molecule treated cancer cells (by 30-50%, p<0.05). Simultaneously, carbon monoxide-releasing molecule and carbon monoxide exposure inhibited tumour proliferation and microvascular density of xenotransplanted tumours (p<0.01), and doubled the survival rates (p<0.005). Exposure of mice to carbon monoxide led to an almost 3-fold increase in carbon monoxide content in tumour tissues (p=0.006).

CONCLUSION:

These data suggest a new biological function for carbon monoxide in carcinogenesis, and point to the potential chemotherapeutic/chemoadjuvant use of carbon monoxide in pancreatic cancer.

KEYWORDS:

Anticancer effects; Heme catabolic pathway; Heme oxygenase

PMID:
24433995
DOI:
10.1016/j.dld.2013.12.007
[Indexed for MEDLINE]

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