| Induction of Thioredoxin by Oxidative Stress and Overexpression of Thioredoxin in Lung Cancer Tissue. |
|
Jang Hoon Lee, Hyung Jung Kim, Chul Min Ahn, Sung Kyu Kim, Won Young Lee |
|
Department of Internal Medicine, Yonsei University College of Medicine, Korea. |
|
|
| Abstract |
BACKGROUND
Reactive oxygen species are involved in multi -stage process of carcinogenesis. The most of cancer cell lines and cancer cells in tumor tissue produce reactive oxygen species and on the other hand, the activities of catalase, Mn - and CuZn-superoxide dismutase in tumor cells are usually low. These persistent oxidative stress in tumor tissue facilitates tumor invasion and metastasis. 12- kDa thioredoxin, which regulate the intracellular redox potential with glutathione and glutaredoxin is involved in cell activation, proliferation, differentiation and re dox- mediated apoptosis. It is also purified as 14 -kDa and 10- kDa eosinophilic cytotoxic enhancing factor(ECEF) from human histiocytic cell(U937) and 10 -kDa ECEF has more than 20 times eosinophilic stimulation activity than 14 - kDa ECEF. It has been reported that adult T-cell leukemia, squamous cell carcinoma of uterine cervix, and hepatocellular carcinoma show increased amounts of human thioredoxin and thioredoxin mRNA is increased in lung cancer. In this study, we investigated the expression of conventional antioxidant enzymes such as catalase, CuZn-SOD, and glutathione peroxidase and thioredoxin in lung cancer tissue compared to adjacent normal lung tissue and the induction of thioredoxin in macrophage cells after treatment of oxidative stress and endotoxin . METHODS: We measured the amount of conventional antioxidant enzymes such as catalase, CuZn-SOD, and glutathione peroxidase and thioredoxin in lung cancer tissue compared to adjacent normal lung tissue by immunoblot analysis and the induction of thioredo xin in mouse monocyte - macrophage cells(RAW 264.7) by treatment of 5 microM menadione and 1 microgram/ml endotoxin. RESULTS: On immunoblot analysis, the expression of 12 -kDa thioredoxin was increased in lung cancer tissue compared to paired normal lung tissue. but th e expression of catalase and CuZn-SOD were decreased in lung cancer tissue compared to paired normal tissue and the expression of glutathione peroxidase in lung cancer was variable. The expression of truncated thioredoxin was also increased in lung cancer. When mouse monocyte - macrophage cells were treated with 5 microM menadione and 1 microG/ml endotoxin, the expression of thioredoxin was peaked at 12 hrs and sustained to 48 hrs. CONCLUSION: In contrast with other conventional antioxidants, the expression of 12-kDa and truncated thioredoxin in lung cancer were increased and it is closely associated with persistent oxidative stress in tumor microenvironment. Considering especially the biological functions of truncated thioredoxin, the increased amount of truncated thioredoxin has significant role in tumor growth through cell proliferation. |
| Key Words:
Oxidative Stress, Antioxidants, Thioredoxin, Lung Cancer |
|
PDF Links
Full text via DOI
Download Citation
