Antiproliferative effects of carbon monoxide on pancreatic cancer
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
24433995
DOI
10.1016/j.dld.2013.12.007
PII: S1590-8658(13)00695-6
Knihovny.cz E-resources
- Keywords
- Anticancer effects, Heme catabolic pathway, Heme oxygenase,
- MeSH
- Carcinoma, Pancreatic Ductal * MeSH
- Phosphorylation drug effects MeSH
- Gasotransmitters pharmacology MeSH
- Humans MeSH
- Mice, Nude MeSH
- Mice MeSH
- Pancreatic Neoplasms * MeSH
- Organometallic Compounds pharmacology MeSH
- Carbon Monoxide pharmacology MeSH
- Cell Proliferation drug effects MeSH
- Proto-Oncogene Proteins c-akt drug effects metabolism MeSH
- Xenograft Model Antitumor Assays MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Gasotransmitters MeSH
- Organometallic Compounds MeSH
- Carbon Monoxide MeSH
- Proto-Oncogene Proteins c-akt MeSH
- tricarbonyldichlororuthenium (II) dimer MeSH Browser
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.
Department of Biochemistry and Microbiology Institute of Chemical Technology Prague 6 Czech Republic
Queen's Medical Research Institute University of Edinburgh Edinburgh UK
References provided by Crossref.org
Carbon Monoxide-Releasing Activity of Plant Flavonoids
Visible-Light-Activated Carbon Monoxide Release from Porphyrin-Flavonol Hybrids
Antiproliferative and Cytotoxic Activities of Fluorescein-A Diagnostic Angiography Dye
Cyanine-Flavonol Hybrids for Near-Infrared Light-Activated Delivery of Carbon Monoxide
Light-Activated Carbon Monoxide Prodrugs Based on Bipyridyl Dicarbonyl Ruthenium(II) Complexes
