Korean J Endocr Surg.
2007 Jun;7(2):69-74. 10.16956/kjes.2007.7.2.69.
Cyclopamine Inhibits Cancer Cell Proliferation in Thyroid Cancer Cell Lines
- Affiliations
-
- 1Departments of Surgery, Chungbuk National University, Cheongju, Korea. webjwpark@chungbuk.ac.kr
- 2Departments of Pediatrics, Chungbuk National University, Cheongju, Korea.
- 3Department of Surgery, Eulji University School of Medicine, Daejeon, Korea.
- 4Department of Surgery, University of California, San Francisco, UCSF/Mount Zion Medical Center, San Francisco, USA.
- KMID: 2375887
- DOI: http://doi.org/10.16956/kjes.2007.7.2.69
Abstract
- PURPOSE
The Hedgehog (HH) signaling pathway is important in development. Recently,ectopic activation of this pathway has been implicated in several forms of solid cancer including basal cell carcinoma, pancreatic cancer, colon cancer, and prostate cancer. There are three HH proteins involved in the pathway: Sonic HH, Indiana HH, and Desert HH. Cyclopamine disrupts Sonic HH signaling by inhibition of the seven-transmembrane receptor Smoothened (SMO). Whereas cyclopamine is cytotoxic to several human cancer cells, its effect on thyroid cancer cellsis unknown. We therefore investigated the effect of cyclopamine on cell proliferation in human thyroid cancer cell lines.
METHODS
We used fivethyroid cancer cell lines: TPC-1 (papillary), FTC-133, FTC-236, FTC-238 (follicular), and XTC-1 (Hurthle cell). The MTT assay and cell cycle analysis were used to evaluate anti-proliferative effects. Tomatidine, a structural analogue of cyclopamine, was used as a control agent. Statistical significance was tested by ANOVA.
RESULTS
After 4 days of treatment, the percent inhibition of growth with a concentration of 5, 10, and 20 M cyclopamine in the cell lines were 23.6±4.9%, 66.4±4.7% and 69.3±1.3% in TPC-1 7.5±2.8%, 10.7±3.2% and 49.6±6.4% in FTC-133, 19.2±9.5%, 50.4±4.8% and 60.4±2.0% in FTC- 236 22.8±4.2%, 53.4±5.5% and 63.7±4.8% in FTC- 238 7.6±5.8%, 16.6±2.2%, 24.0±4.3% in XTC-1. Treatment with tomatidine at the same concentrations did not significantly affect cell growth. Exposure to cyclopamine, however, did not affect the cell cycle significantly
CONCLUSION
Cyclopamine inhibits cancer cell proliferation in a dose dependent manner in thyroid cancer cell lines. The Hh signaling pathway might be a useful therapeutic target for thyroid cancer.
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