Reversine induces cell cycle arrest, polyploidy, and apoptosis in human breast cancer cells.

Abstract

BACKGROUND:

Reversine, a small synthetic purine analogue, has been reported to be effective in tumor suppression. In the present study, we demonstrated an antitumor activity of reversine that could suppress cellular proliferation and induce cell cycle arrest and apoptosis in human breast cancer cell lines.

METHODS:

To evaluate whether reversine could suppress cell growth of MCF-7 and MDA-MB-231 cells and induce cell death, the cell viability, cell cycle, and apoptosis were determined in this study.

RESULTS:

Reversine treatment in human breast cancer cells reduced cell viability in a dose-dependent manner. Cell cycle accumulation at the G2/M phase in reversine-treated cells was also determined. Moreover, polyploidy was also found in reversine-treated cells. Apoptosis in reversine-treated cells was exhibited with PARP cleavage and caspase-3 and caspase-8 activation, but not caspase-9 activation, indicating that caspase-dependent apoptosis mediated by an extrinsic pathway took place in reversine-treated cells. Furthermore, reversine attenuated cell death in cells pretreated with a pan-caspase inhibitor before reversine treatment.

CONCLUSIONS:

In the present study, we demonstrated that reversine contributes to growth inhibition in human breast cancer cells through cell cycle arrest, polyploidy, and/or apoptosis induction. The apoptosis mediated by reversine was induced by the mitochondria-independent pathway. Therefore, the potential role of reversine as a novel therapeutic agent for the treatment of breast cancer is worthy of further investigation.

• Authors: Chin-Ho Kuo, Yin-Che Lu, Ya-Shin Tseng, Chung-Sheng Shi, Shu-Hsin Chen, Ping-Tzu Chen, Feng-Ling Wu, Yi-Ping Chang, Ying-Ray Lee
• Journal: Breast cancer (Tokyo, Japan) (Breast Cancer) Vol. 21 Issue 3 Pg. 358-69 (May 2014) ISSN: 1880-4233 [Electronic] Japan
• PMID: 22926505 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Morpholines
• Purines
• 2-(4-morpholinoanilino)-6-cyclohexylaminopurine

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Breast Neoplasms (drug therapy, genetics, metabolism, pathology)
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor (drug effects)
• Drug Screening Assays, Antitumor
• Female
• Humans
• MCF-7 Cells (drug effects)
• Mitochondria (drug effects)
• Morpholines (pharmacology)
• Polyploidy
• Purines (pharmacology)