Reversine, a 2,6-disubstituted purine, as an anti-cancer agent in differentiated and undifferentiated thyroid cancer cells.

Abstract

PURPOSE:

A novel and effective treatment is urgently needed to deal with the current treatment dilemma in incurable differentiated thyroid cancer (DTC), poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC). Reversine, a small synthetic purine analogue (2,6-disubstituted purine), has been shown to be effective in tumor suppression.

METHODS:

We performed in vitro evaluation of anti-tumor effects of reversine on proliferation, cell cycle, and apoptosis in human PDTC, ATC, and follicular thyroid cancer cell lines, respectively.

RESULTS:

Treatment of these three lines with reversine inhibited proliferation in a time- and dose-dependent manner. G2/M accumulation was demonstrated in cell cycle analysis. Reversine induced apoptosis in PDTC cells with caspase-3 and caspase-8 activation, but not caspase-9. Use of a pan-caspase inhibitor before treatment with reversine attenuated cell death. Reversine also showed in vivo growth inhibitory effects on ATC cells in a xenograft nude mice model.

CONCLUSIONS:

Data demonstrated that reversine is effective in inhibiting the growth of thyroid cancer cells by cell cycle arrest or apoptosis, especially with the more aggressive ATC and PDTC. Apoptosis was induced by the mitochondria-independent pathway. Reversine is therefore worthy of further investigation in clinical therapeutics.

• Authors: Shih-Che Hua, Tien-Chun Chang, Hau-Ren Chen, Chieh-Hsiang Lu, Yi-Wen Liu, Shu-Hsin Chen, Hui-I Yu, Yi-Ping Chang, Ying-Ray Lee
• Journal: Pharmaceutical research (Pharm Res) Vol. 29 Issue 7 Pg. 1990-2005 (Jul 2012) ISSN: 1573-904X [Electronic] United States
• PMID: 22477067 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Purines
• Caspase 3
• Caspase 8
• Caspase 9

Topics

• Animals
• Antineoplastic Agents (chemistry, pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Caspase 8 (metabolism)
• Caspase 9 (metabolism)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Purines (chemistry, pharmacology, therapeutic use)
• Thyroid Carcinoma, Anaplastic
• Thyroid Gland (drug effects, metabolism, pathology)
• Thyroid Neoplasms (drug therapy, metabolism, pathology)