Inhibition of Importin β1 With a 2-Aminothiazole Derivative Resulted in G/M Cell-cycle Arrest and Apoptosis.

Background: The design and synthesis of novel chemotherapeutic agents that can induce apoptosis and cell-cycle arrest has emerged as an attractive approach for the treatment of cancer, because they can limit possible nonspecific effects of compound treatment. Previous studies established that the expression of KPNB1 was increased in several cancer cells and transformed cell lines and inhibition of KPNB1 using siRNA significantly inhibited cervical tumour proliferation, but did not affect normal cervical epithelium. Recently, we reported that a KPNB1 inhibitor, the 2-aminothiazole derivative 1, possesses strong anti-proliferative effects against several cancer cells in the nanomolar concentration range.

Results: Treatment with compound 1 interferes with cell-cycle progression in the G/M phase, as detected by flow cytometry analysis and results in apoptosis by the intrinsic pathway. Fluorescence microscopic analysis of mitotic cells predominantly mitotic abnormal cells with monopolar spindles and treatment with compound 1 did not affect polymerization of microtubules.

Conclusion: Compound 1, as a KPNB1 inhibitor, might be a good target for future development of anticancer agents showing the activities of apoptosis and cell cycle arrest.