Radiosensitizer sanazole (AK-2123) enhances gamma-radiation-induced apoptosis in murine fibrosarcoma

Sanazole (AK-2123) (N-2'-methoxy ethyl)-2-(3"-nitro-1"-triazolyl)acetamide, which has completed phase III clinical trials as a radiosensitizer, enhanced gamma-radiation induced apoptosis in murine fibrosarcoma upon i.p. administration at 40 mg/kg body weight one hour prior to irradiat...

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Bibliographic Details
Published in:Journal of radiation research 2003-12, Vol.44 (4), p.359-365
Main Authors: Rajagopalan, Rema, Kagiya, Tsutomu V, Nair, Cherupally Krishnan Krishnan
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Caspase 3
Caspases - biosynthesis
Cell Nucleus - metabolism
DNA Fragmentation
Fibrosarcoma - pathology
Gamma Rays
Genome
Male
Mice
Neoplasm Transplantation
Neoplasms, Radiation-Induced - pathology
Nucleosomes - metabolism
Radiation-Sensitizing Agents - pharmacology
Sarcoma, Experimental - pathology
Time Factors
Triazoles - pharmacology
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Summary:Sanazole (AK-2123) (N-2'-methoxy ethyl)-2-(3"-nitro-1"-triazolyl)acetamide, which has completed phase III clinical trials as a radiosensitizer, enhanced gamma-radiation induced apoptosis in murine fibrosarcoma upon i.p. administration at 40 mg/kg body weight one hour prior to irradiation. A microscopic examination of Giemsa-May-Grunwald stained cells has shown a higher frequency of condensed nuclei and fragmented nuclei in the tumor cells. The administration of sanazole to tumor-bearing animals enhanced the radiation-induced internucleosomal fragmentation in the nuclear genome of tumor cells. Higher levels of caspase-3 activity were also observed in the cell extracts of tumours from AK-2123 administered mice. Exposure to gamma-radiation of AK-2123-treated mouse further enhanced the caspase-3 activity, indicating the induction of apoptosis. The radiation sensitization property of sanazole was discernible by comparing the relative tumor diameter following irradiation after i.p. administration of AK-2123 and irradiation alone; it was higher during the first few days followed by the treatment.
ISSN:0449-3060
DOI:10.1269/jrr.44.359