Antiproliferative effects of carbon monoxide on pancreatic cancer

Libor Vítek, Helena Gbelcová, Lucie Muchová, Kateřina Váňová, Jaroslav Zelenka, Renata Koníčková, Jakub Šuk, Marie Zadinova, Zdeněk Knejzlík, Shakil Ahmad, Takeshi Fujisawa, Asif Ahmed, Tomáš Ruml

Research output: Contribution to journalArticle

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. © 2013 Editrice Gastroenterologica Italiana S.r.l.

LanguageEnglish
Pages369-375
Number of pages7
JournalDigestive and Liver Disease
Volume46
Issue number4
DOIs
Publication statusPublished - Apr 2014

Fingerprint

Carbon Monoxide
Pancreatic Neoplasms
Neoplasms
Heme Oxygenase (Decyclizing)
Nude Mice

Bibliographical note

Funding: Czech Ministry of Health (conceptual development of research organization RVO-VFN64165/2013); Czech Ministry of Education (LH11030); and Charles University in Prague (PRVOUK-P25/LF1/2, SVV 266516/2013)

Keywords

  • anticancer effects
  • Heme catabolic pathway
  • Heme oxygenase

Cite this

Vítek, L., Gbelcová, H., Muchová, L., Váňová, K., Zelenka, J., Koníčková, R., ... Ruml, T. (2014). Antiproliferative effects of carbon monoxide on pancreatic cancer. Digestive and Liver Disease, 46(4), 369-375. https://doi.org/10.1016/j.dld.2013.12.007
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. / Antiproliferative effects of carbon monoxide on pancreatic cancer. In: Digestive and Liver Disease. 2014 ; Vol. 46, No. 4. pp. 369-375.
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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. {\circledC} 2013 Editrice Gastroenterologica Italiana S.r.l.",
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Vítek, L, Gbelcová, H, Muchová, L, Váňová, K, Zelenka, J, Koníčková, R, Šuk, J, Zadinova, M, Knejzlík, Z, Ahmad, S, Fujisawa, T, Ahmed, A & Ruml, T 2014, 'Antiproliferative effects of carbon monoxide on pancreatic cancer' Digestive and Liver Disease, vol. 46, no. 4, pp. 369-375. https://doi.org/10.1016/j.dld.2013.12.007

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; Ruml, Tomáš.

In: Digestive and Liver Disease, Vol. 46, No. 4, 04.2014, p. 369-375.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Antiproliferative effects of carbon monoxide on pancreatic cancer

AU - Vítek, Libor

AU - Gbelcová, Helena

AU - Muchová, Lucie

AU - Váňová, Kateřina

AU - Zelenka, Jaroslav

AU - Koníčková, Renata

AU - Šuk, Jakub

AU - Zadinova, Marie

AU - Knejzlík, Zdeněk

AU - Ahmad, Shakil

AU - Fujisawa, Takeshi

AU - Ahmed, Asif

AU - Ruml, Tomáš

N1 - Funding: Czech Ministry of Health (conceptual development of research organization RVO-VFN64165/2013); Czech Ministry of Education (LH11030); and Charles University in Prague (PRVOUK-P25/LF1/2, SVV 266516/2013)

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N2 - 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. © 2013 Editrice Gastroenterologica Italiana S.r.l.

AB - 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. © 2013 Editrice Gastroenterologica Italiana S.r.l.

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KW - Heme catabolic pathway

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Vítek L, Gbelcová H, Muchová L, Váňová K, Zelenka J, Koníčková R et al. Antiproliferative effects of carbon monoxide on pancreatic cancer. Digestive and Liver Disease. 2014 Apr;46(4):369-375. https://doi.org/10.1016/j.dld.2013.12.007