Abstract | OBJECTIVE: MATERIAL AND METHODS: Mouse and human fibrosarcoma (Wehi164; HT1080) cells were treated with D7, alone, or in combination with radiation, for determination of cytotoxicity, clonogenic survival, and apoptotic death assays. Involvement of oxidative mechanism and nuclear factor kappa B ( NF-kappaB) was studied in different treatment groups. In addition, fibrosarcoma-bearing mice were treated with D7 (intravenously, two doses, each of 1 mg/kg body weight) combined with radiation (two fractions of 2.5 Gy each) at appropriate intervals. The tumor volume was measured to assess ' tumor growth delay', and liver function enzymes in the serum of mice were estimated after the treatments. RESULTS: A combination treatment with D7 and radiation showed enhancement in cytotoxicity and apoptotic induction and decrease in clonogenic survival of tumor cells, as compared to the treatments with the drug or radiation alone. Moreover, D7 in combination with radiation could significantly inhibit the radiation-induced NF-kappaB activation, and showed the generation of comparatively more intracellular reactive oxygen species (ROS). Similarly, a combination of D7 and radiation in vivo caused significant inhibition of tumor growth in vivo, and restoring the liver enzyme activity to the 'normal' level. CONCLUSION: The combined treatment with quinonoid D7 and radiation caused increased cytotoxicity compared to single treatment with either agent alone in fibrosarcoma tumor systems, both in vitro and in vivo.
|
Authors | Binod Kumar, Amit Kumar, B N Pandey, Banasri Hazra, K P Mishra |
Journal | International journal of radiation biology
(Int J Radiat Biol)
Vol. 84
Issue 5
Pg. 429-40
(May 2008)
ISSN: 0955-3002 [Print] England |
PMID | 18464072
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- NF-kappa B
- Naphthoquinones
- Radiation-Sensitizing Agents
- Reactive Oxygen Species
- diospyrin diethylether
|
Topics |
- Animals
- Apoptosis
- Cell Death
- Cell Line, Tumor
- Cell Proliferation
- Cell Survival
- Dose-Response Relationship, Radiation
- Fibrosarcoma
(drug therapy)
- Humans
- Mice
- NF-kappa B
(metabolism)
- Naphthoquinones
(pharmacology)
- Radiation Tolerance
- Radiation-Sensitizing Agents
(pharmacology)
- Reactive Oxygen Species
|