Abstract | INTRODUCTION:
Survivin, an inhibitor of apoptosis protein and key regulator of mitosis, is up-regulated in a variety of cancers and is often associated with a worse prognosis. Terameprocol down-regulates the Sp1-mediated transcription of survivin and Cdk1, which is important for cell cycle progression and many other proteins. Survivin inhibition has previously been shown to result in the induction of apoptosis and radiosensitization. METHODS: This study examined the effects of terameprocol administration on survivin transcription and expression in HCC2429 and H460 lung cancer cells. We also examined the combined effects of radiation and terameprocol on apoptosis and radiosensitivity. RESULTS: Using immunoblot analysis and luciferase assays, we confirmed that terameprocol decreases survivin transcription and protein expression. Ultimately, however, decreases in survivin expression failed to correlate with an increase in apoptosis. Nonetheless, clonogenic assay revealed that terameprocol induces increased radiosensitization in HCC2429 (dose enhancement ratio = 1.26, p = 0.019) and H460 (dose enhancement ratio = 1.18, p = 0.001) cells. Additionally, the data show no effect of terameprocol on cell cycle in either HCC2429 or H460 cells. CONCLUSIONS:
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Authors | Yunguang Sun, Nicholas J Giacalone, Bo Lu |
Journal | Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
(J Thorac Oncol)
Vol. 6
Issue 1
Pg. 8-14
(Jan 2011)
ISSN: 1556-1380 [Electronic] United States |
PMID | 21107289
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- BIRC5 protein, human
- Inhibitor of Apoptosis Proteins
- Radiation-Sensitizing Agents
- Sp1 Transcription Factor
- Survivin
- terameprocol
- Masoprocol
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Topics |
- Apoptosis
(drug effects, radiation effects)
- Blotting, Western
- Carcinoma, Non-Small-Cell Lung
(pathology, radiotherapy)
- Cell Cycle
(drug effects, radiation effects)
- Cell Proliferation
(drug effects, radiation effects)
- Gene Expression Regulation, Neoplastic
(drug effects)
- Humans
- Inhibitor of Apoptosis Proteins
(genetics, metabolism)
- Lung Neoplasms
(pathology, radiotherapy)
- Masoprocol
(analogs & derivatives, pharmacology)
- Radiation-Sensitizing Agents
(pharmacology)
- Sp1 Transcription Factor
(metabolism)
- Survivin
- Tumor Cells, Cultured
- Tumor Stem Cell Assay
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