Libor Vítek1, Helena Gbelcová2, Lucie Muchová3, Kateřina Váňová3, Jaroslav Zelenka3, Renata Koníčková3, Jakub Suk3, Marie Zadinova3, Zdeněk Knejzlík2, Shakil Ahmad4, Takeshi Fujisawa5, Asif Ahmed4, Tomáš Ruml6. 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.
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 humanpancreatic cancer. METHODS: In vitro studies were performed on humanpancreatic 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 humanpancreatic 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.
Authors: Mariapaola Nitti; Sabrina Piras; Umberto M Marinari; Lorenzo Moretta; Maria A Pronzato; Anna Lisa Furfaro Journal: Antioxidants (Basel) Date: 2017-05-05
Authors: Zsuzsanna Nemeth; Eva Csizmadia; Lisa Vikstrom; Mailin Li; Kavita Bisht; Alborz Feizi; Sherrie Otterbein; Brian Zuckerbraun; Daniel B Costa; Pier Paolo Pandolfi; Janos Fillinger; Balazs Döme; Leo E Otterbein; Barbara Wegiel Journal: Oncotarget Date: 2016-04-26