| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Vítek, Libor Gbelcová, Helena Muchová, Lucie Vánová, Katerina Zelenka, Jaroslav Konícková, Renata Suk, Jakub Zadinova, Marie Knejzlík, Zdenek Ahmad, Shakil Fujisawa, Takeshi Ahmed, Asif Ruml, Tomás |
| Description |
Author Affiliation: Vítek L ( Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, Prague 2, Czech Republic); Gbelcová H ( Department of Biochemistry and Microbiology, Institute of Chemical Technology, Prague 6, Czech Republic.); Muchová L ( Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, Prague 2, Czech Republic.); Vánová K ( Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, Prague 2, Czech Republic.); Zelenka J ( Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, Prague 2, Czech Republic.); Konícková R ( Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, Prague 2, Czech Republic.); Suk J ( Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, Prague 2, Czech Republic.); Zadinova M ( Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, Prague 2, Czech Republic.); Knejzlík Z ( Department of Biochemistry and Microbiology, Institute of Chemical Technology, Prague 6, Czech Republic.); Ahmad S ( Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK); Fujisawa T ( Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.); Ahmed A ( Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK); Ruml T ( 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. |
| File Format |
HTM / HTML |
| ISSN |
15908658 |
| Issue Number |
4 |
| Volume Number |
46 |
| e-ISSN |
18783562 |
| Journal |
Digestive and Liver Disease |
| Language |
English |
| Publisher |
Elsevier |
| Publisher Date |
2014-04-01 |
| Publisher Place |
Netherlands |
| Access Restriction |
One Nation One Subscription (ONOS) |
| Subject Keyword |
Discipline Gastroenterology Carbon Monoxide Pharmacology Carcinoma, Pancreatic Ductal Cell Proliferation Drug Effects Gasotransmitters Organometallic Compounds Pancreatic Neoplasms Phosphorylation Proto-oncogene Proteins C-akt Animals Humans Mice Mice, Nude Metabolism Xenograft Model Antitumor Assays Journal Article Research Support, Non-u.s. Gov't |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Hepatology Gastroenterology |
