Antiproliferative effects of carbon monoxide on pancreatic cancer

Vítek, Libor, Gbelcová, Helena, Muchová, Lucie, Váňová, Kateřina, Zelenka, Jaroslav, Koníčková, Renata, Šuk, Jakub, Zadinova, Marie, Knejzlík, Zdeněk, Ahmad, Shakil, Fujisawa, Takeshi, Ahmed, Asif and Ruml, Tomáš (2014). Antiproliferative effects of carbon monoxide on pancreatic cancer. Digestive and liver disease, 46 (4), pp. 369-375.

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/24 h). 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 1 h/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.

Divisions: Life & Health Sciences > Biosciences
Life & Health Sciences
Additional Information: Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
Uncontrolled Keywords: anticancer effects, Heme catabolic pathway, Heme oxygenase
Published Date: 2014-04
Authors: Vítek, Libor
Gbelcová, Helena
Muchová, Lucie
Váňová, Kateřina
Zelenka, Jaroslav
Koníčková, Renata
Šuk, Jakub
Zadinova, Marie
Knejzlík, Zdeněk
Ahmad, Shakil
Fujisawa, Takeshi
Ahmed, Asif
Ruml, Tomáš

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