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

Abstract

Induction of haem oxygenase-1 (HO-1) may provide an important protective effect for cells against oxidative stress. Here, we investigated the mechanism of cytoprotection of HO-1 in solid tumour with a focus on the antiapoptotic activity of HO-1. Treatment of rat hepatoma AH136B cells with the HO 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 HO-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.

Nuclear Heme Oxygenase-1 (HO-1) Modulates Subcellular Distribution and Activation of Nrf2, Impacting Metabolic and Anti-oxidant Defenses

“…HO-1 has long been identified as proto-oncogenic due to its anti-apoptotic and pro-angiogenic properties (54,55), and there is a positive relationship between high nuclear HO-1 content and severity of prostate cancer (35), Nonetheless, the precise role of HO-1 in cancer biology is far from being completely understood. Cancer cells display altered metabolic circuitry and nutrient uptake to increase proliferation preferentially, leading to glucose-dependent ATP production (Warburg theory).…”

CD4+CD25+FoxP3+ T-cell infiltration and heme oxygenase-1 expression correlate with tumor grade in human gliomas

“…These are significant findings, which elucidate the mechanism of HO-1 induction and expression in human gliomas. HO-1 has an important role in rapid tumor growth because of its antioxidative and antiapoptotic effects [29,30]. Indeed, there is convincing evidence that accumulation of HO-1 expressing macrophages in necrotic areas of malignant brain tumors contributes to neoplastic growth and tissue damage [24].…”

Resolvin D1 reduces deterioration of tight junction proteins by upregulating HO-1 in LPS-induced mice

“…41 Early study clearly demonstrated that HO-1 induced by NO had a potent anti-apoptotic function in an experimental AH136B solid tumor in rats and Znpp IX induced the apoptosis of AH136B cells both in vivo and in vitro through inhibition of HO-1 activity. 42 HO-1 attenuates glucose-mediated cell growth arrest and apoptosis in human micro-vessel endothelial cells. 43 These may explain why mice pretreated with RvD1 showed higher expression of HO-1 and TJ proteins and decrease of apoptosis cells in TUNEL compared with the LPS group in this study.…”