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

Abstract

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.

• Authors: Rema Rajagopalan, Tsutomu V Kagiya, Cherupally Krishnan Krishnan Nair
• Journal: Journal of radiation research (J Radiat Res) Vol. 44 Issue 4 Pg. 359-65 (Dec 2003) ISSN: 0449-3060 [Print] England
• PMID: 15031563 (Publication Type: Journal Article)

Chemical References

• Nucleosomes
• Radiation-Sensitizing Agents
• Triazoles
• AK 2123
• Casp3 protein, mouse
• Caspase 3
• Caspases

Topics

• 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)