J Korean Surg Soc.
2009 Jun;76(6):337-347. 10.4174/jkss.2009.76.6.337.
Effect of Combination of Anticancer Agents and Nitroimidazoles on the Survival of Human Hepatocellular Carcinoma Cells under Hypoxic Conditions
- Affiliations
-
- 1Department of Biochemistry, College of Medicine, Catholic University of Daegu, Korea. leejw@cu.ac.kr
- 2Department of Surgery, College of Medicine, Catholic University of Daegu, Korea. shwpark@cu.ac.kr
- 3Department of Laboratory Medicine, College of Medicine, Catholic University of Daegu, Korea.
- 4Department of Pathology, College of Medicine, Catholic University of Daegu, Korea.
- 5Ansim Internal Medicine Clinic, Daegu, Korea.
- 6Department of Biochemistry, College of Medicine, Keimyung University, Daegu, Korea.
- KMID: 1464948
- DOI: http://doi.org/10.4174/jkss.2009.76.6.337
Abstract
-
PURPOSE: In a previous study, we have shown that anticancer agents inhibiting topoisomerases improve survival of tumor cells under hypoxic condition. In the present study, we evaluated whether and how cell survival effect of the anticancer agents under hypoxic conditions could be eliminated by the addition of nitroimidazoles, a class of bioreductive agents.
METHODS
Human hepatocellular carcinoma cells (HepG2) were incubated with different combinations of pimonidazole (1~1,000 microg/ml) and doxorubicin (0.1 or 1 microg/ml) concentrations under different O2 concentrations [1, 3, 5, 10 and 21 O2]. Then cell numbers, glucose concentrations and lactic acid concentrations in the medium were measured, and DNA fragmentation assay was performed. Finally, different combinations of nitroimidazoles, such as pimonidazole, misonidazole, etanidazole, tinidazole, metronidazole, ornidazole or dimetridazole, and anticancer agents, such as doxorubicin, campothecin, epirubicin, dactinomycin, etoposide or mitomycin C was added to the cell culture medium under hypoxic conditions (1% O2).
RESULTS
Pimonidazole at a concentration of 100 microg/ml eliminated cell survival effect of doxorubicin at the concentrations of 0.1 and 1 microg/ml under hypoxic condition (1% O2) by promoting apoptosis. Almost all the cells died even after 24 hours of incubation for all the oxygen concentrations at a combination of 100 microg/ml pimonidazole and 1 microg/ml doxorubicin. Finally, pimonidazole at a concentration of 100 microg/ml, and misonidazole or etanidazole at a concentration of 1,000 microg/ml eliminated cell survival effect of all the anticancer agents tested under hypoxic condition.
CONCLUSION
Combination therapy of doxorubicin (adriamycin) with pimonidazole can maximize dororubicin efficacy by eliminating cell survival effect of doxorubicin under hypoxic conditions in treating solid tumors, such as breast cancer.
MeSH Terms
-
Anoxia
Antineoplastic Agents
Apoptosis
Breast Neoplasms
Carcinoma, Hepatocellular
Cell Count
Cell Culture Techniques
Cell Survival
Dactinomycin
Dimetridazole
DNA Fragmentation
Doxorubicin
Epirubicin
Etanidazole
Etoposide
Glucose
Humans
Lactic Acid
Metronidazole
Misonidazole
Mitomycin
Nitroimidazoles
Ornidazole
Oxygen
Tinidazole
Antineoplastic Agents
Dactinomycin
Dimetridazole
Doxorubicin
Epirubicin
Etanidazole
Etoposide
Glucose
Lactic Acid
Metronidazole
Misonidazole
Mitomycin
Nitroimidazoles
Ornidazole
Oxygen
Tinidazole
- Full Text Links
-
- Actions
-
Cited
- CITED
-
- Close
- Share
-
- Similar articles
-
- Effect of antitumor agents on the survival of human hepatocellular carcinoma cells under hypoxic conditions
- Effect of Antibiotics on the Survival of Human Hepatocellular Carcinoma Cells under Hypoxic Conditions
- Effect of anticancer drugs and desferrioxamine in combination with radiation on hepatoma cell lines
- Everolimus Plus Ku0063794 Regimen Promotes Anticancer Effects against Hepatocellular Carcinoma Cells through the Paradoxical Inhibition of Autophagy
- CaMKII Inhibitor KN-62 Blunts Tumor Response to Hypoxia by Inhibiting HIF-1alpha in Hepatoma Cells
