In vitro hypoxic cytotoxicity and hypoxic radiosensitization. Efficacy of the novel 2-nitroimidazole N,N,N-tris[2-(2-nitro-1H-imidazol-1-yl)ethyl]amine.

Abstract

BACKGROUND AND PURPOSE:

Tumor hypoxia is a major problem in radiation therapy of solid tumors because of the radiosensitizing effect of oxygen. Nitroimidazole-containing compounds are oxygen mimetics accumulating in hypoxic tumor areas. However, the broad use of 2-nitroimidazoles as a hypoxic radiosensitizer is limited by their partially low efficacy and/or high neurotoxicity.

MATERIALS AND METHODS:

Here, we characterized the in vitro hypoxic cytotoxicity and hypoxic radiosensitizing efficacy of N,N,N-tris [2-(2-nitro-1H-imidazol-1-yl)ethyl]amine (PRC) in a hypoxia-sensitive lymphoma and a hypoxia-resistant glioblastoma cell line by colony formation assay and flow cytometry.

RESULTS:

PRC exerted high hypoxic cytotoxic and radiosensitizing action on both cell lines at almost absent toxicity under normoxic conditions. In particular, under hypoxia, but not normoxia, PRC targeted the mitochondria resulting in oxidative stress, G(2)/M cell cycle arrest, and triggering of the intrinsic apoptosis pathway.

CONCLUSION:

Our in vitro findings suggest that PRC might be a promising new 2-nitroimidazole for improving radiation therapy of hypoxic tumors in vivo.

• Authors: M Langenbacher, R J Abdel-Jalil, W Voelter, M Weinmann, S M Huber
• Journal: Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] (Strahlenther Onkol) Vol. 189 Issue 3 Pg. 246-54 (Mar 2013) ISSN: 1439-099X [Electronic] Germany
• PMID: 23361139 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Ethylamines
• N,N,N-tris(2-(2-nitro-1H-imidazol-1-yl)ethyl)amine
• Nitroimidazoles
• Radiation-Sensitizing Agents
• Reactive Oxygen Species

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Hypoxia (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Ethylamines (pharmacology)
• Flow Cytometry
• Humans
• In Vitro Techniques
• Jurkat Cells
• Mitochondria (drug effects)
• Nitroimidazoles (pharmacology)
• Radiation-Sensitizing Agents (pharmacology)
• Reactive Oxygen Species
• Tumor Stem Cell Assay