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

Research output: Contribution to journalArticlepeer-review

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. (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
Volume46
Issue number4
DOIs
Publication statusPublished - Apr 2014

Keywords

  • Anticancer effects
  • Heme catabolic pathway
  • Heme oxygenase
  • NITRIC-OXIDE SYNTHASE
  • MEDIATED ANGIOGENESIS
  • HEME OXYGENASE-1
  • ENDOTHELIAL-CELLS
  • IN-VIVO
  • EXPRESSION
  • AKT
  • INHIBITION
  • ACTIVATION
  • CHEMOTHERAPY

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