Antiproliferative effects of carbon monoxide on pancreatic cancer

Libor Vitek*, Helena Gbelcova, Lucie Muchova, Katerina Vanova, Jaroslav Zelenka, Renata Konickova, Jakub Suk, Marie Zadinova, Zdenek Knejzlik, Shakil Ahmad, Takeshi Fujisawa, Asif Ahmed, Tomas Ruml

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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. (C) 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)369-375
Number of pages7
JournalDigestive and Liver Disease
Issue number4
Publication statusPublished - Apr 2014

Keywords / Materials (for Non-textual outputs)

  • Anticancer effects
  • Heme catabolic pathway
  • Heme oxygenase
  • AKT


Dive into the research topics of 'Antiproliferative effects of carbon monoxide on pancreatic cancer'. Together they form a unique fingerprint.

Cite this