Antiapoptotic effect of haem oxygenase-1 induced by nitric oxide in experimental solid tumour

S. Tanaka, T. Akaike, J. Fang, T. Beppu, M. Ogawa, F. Tamura, Y. Miyamoto, H. Maeda

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150 Citations (Scopus)


Induction of haem oxygenase-1 (HQ-1) may provide an important protective effect for cells against oxidative stress. Here, we investigated the mechanism of cytoprotection of HQ-1 in solid tumour with a focus on the antiapoptotic activity of HQ-1. Treatment of rat hepatoma AH136B cells with the HQ inhibitor-zinc protoporphyrin IX (ZnPP IX) or tin protoporphyrin IX resulted in extensive apoptotic changes of tumour cells both in vivo and in vitro. Caspase-3 activity of the ZnPP IX-treated hepatoma cells increased significantly. Moreover, ZnPP IX-induced apoptosis was completely inhibited by simultaneous incubation with a specific caspase-3 inhibitor and was partially abrogated by bilirubin, a reaction product of HO. In vivo ZnPP IX treatment did not affect nitric oxide (NO) production and tumour blood flow. Western blot analyses showed that HQ-1 expression in AH136B cells was strongly upregulated by NO donors, for example, S-nitroso-N-acetyl penicillamine and propylamine NONOate in vitro; conversely, it was remarkably reduced in vivo by pharmacological blockade of NOS. We conclude that HO-1 may function in antiapoptotic defense of the tumour, and thus it may have important protective and beneficial effects for tumour cells against oxidative stress induced by NO, which is produced in excess during solid tumour growth in vivo.

Original languageEnglish
Pages (from-to)902-909
Number of pages8
JournalBritish Journal of Cancer
Issue number6
Publication statusPublished - 2003 Mar 24


  • Antiapoptosis
  • Haem oxygenase
  • Nitric oxide
  • Oxidative stress
  • Tumour growth


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