Faculty Collaboration Database

Terameprocol (tetra-O-methyl nordihydroguaiaretic acid), an inhibitor of Sp1-mediated survivin transcription, induces radiosensitization in non-small cell lung carcinoma. J Thorac Oncol 2011 Jan;6(1):8-14

Date

11/26/2010

Pubmed ID

21107289

Pubmed Central ID

PMC3010256

DOI

10.1097/JTO.0b013e3181fa646a

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: Terameprocol significantly enhances the sensitivity of non-small cell lung carcinoma cell lines to radiation therapy, although the mechanism of action remains unclear. Further study is warranted to assess the potential of terameprocol as an agent that may enhance the therapeutic ratio of radiotherapy in lung cancer.

Author List

Sun Y, Giacalone NJ, Lu B

Author

Yunguang Sun MD, PhD Assistant Professor in the Pathology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Apoptosis
Blotting, Western
Carcinoma, Non-Small-Cell Lung
Cell Cycle
Cell Proliferation
Gene Expression Regulation, Neoplastic
Humans
Inhibitor of Apoptosis Proteins
Lung Neoplasms
Masoprocol
Radiation-Sensitizing Agents
Sp1 Transcription Factor
Tumor Cells, Cultured
Tumor Stem Cell Assay