Endocrine Abstracts (2011) 26 P457

Reversine, an anti-cancer candidate, induces cell cycle arrest and apoptosis in human thyroid cancer

Ying-Ray Lee1, Shih-Che Hua2, Shu-Hsin Chen1, Chieh-Hsiang Lu2, Hui-I Yu2, Hau-Ren Chen3 & Tien-Chun Chang4

1Department of Medical Research, Chiayi Christian Hospital, Chiayi City, Taiwan; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Chiayi Christian Hospital, Chiayi City, Taiwan; 3Department of Life Science, Institute of Molecular Biology, National Chung Cheng University, Chiayi, Taiwan; 4Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei City, Taiwan.

Thyroid cancer is the most prevalent cancer among endocrine malignancies. Surgical resection combined with radioactive iodine therapy has been proved effective in treating differentiated thyroid cancer, including papillary and follicular thyroid cancers. However, regarding metastatic poorly differentiated or anaplastic thyroid cancers, there have been no available effective treatment modalities. The genomic instability, such as chromosome aneupolidy, represents a hallmark of solid cancers including thyroid carcinomas, and it has been suggested to underlie the progression to more aggressive phenotypes. Aurora kinase is now thought to play a role in tumor genetic instability and has been found to be altered in human cancer tissues. Several studies disclosed that aurora kinases were overexpressed in thyroid cancers and increased with the dedifferentiation extent.

Reversine, a purine analogue, has reported to inhibit aurora kinases and the phosphorylation of histone H3. Through this mechanism, reversine was shown inhibiting colony formation of leukemic cells from patients with acute myeloid leukemia. However, up to date, no reports aimed to thyroid cancer treatment by using reversine. Besides, there has been no study to investigate its cancer cell death mechanism.

In this study, we revealed that reversine could inhibit thyroid cancer tumor growth and inducing apoptosis. Firstly, we determined the cellular viability of reversine in human thyroid cancer cell lines. Furthermore, we found that reversine could induce cell cycle arrest in these cells. In addition, apoptosis was also be revealed in reversine treated cells. Moreover, the extrinsic pathway was demonstrated to involve in reversine mediated apoptosis. Finally, the xenograft nude mice model was used to prove reversine’s anti-tumor effect in vivo. In the present study, we demonstrated that reversine could be a chemo-therapeutic candidate for human thyroid cancers.

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