CIP-36, a novel topoisomerase II-targeting agent, induces the apoptosis of multidrug-resistant cancer cells in vitro.

Abstract

The need to overcome cancer multidrug resistance (MDR) has fueled considerable interest in the development of novel synthetic antitumor agents with cytotoxicity against cancer cell lines with MDR. In this study, we aimed to investigate CIP-36, a novel podophyllotoxin derivative, for its inhibitory effects on human cancer cells from multiple sources, particularly cells with MDR in vitro. The human leukemia cell line, K562, and the adriamycin-resistant subline, K562/A02, were exposed to CIP-36 or anticancer agents, and various morphological and biochemical properties were assessed by Hoechst 33342 staining under a fluorescence microscope. Subsequently, cytotoxicity, cell growth curves and the cell cycle were analyzed. Finally, the effects of CIP-36 on topoisomerase IIα (Topo IIα) activity were determined. Treatment with CIP-36 significantly inhibited the growth of the K562 and MDR K562/A02 cells. Our data demonstrated that CIP-36 induced apoptosis, inhibited cell cycle progression and inhibited Topo IIα activity. These findings suggest that CIP-36 has the potential to overcome the multidrug resistance of K562/A02 cells by mediating Topo IIα activity.

• Authors: Bo Cao, Hong Chen, Ying Gao, Cong Niu, Yuan Zhang, Ling Li
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 35 Issue 3 Pg. 771-6 (Mar 2015) ISSN: 1791-244X [Electronic] Greece
• PMID: 25592869 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Antineoplastic Agents
• CIP-36
• DNA-Binding Proteins
• Topoisomerase II Inhibitors
• DNA Topoisomerases, Type II
• Podophyllotoxin

Topics

• Antigens, Neoplasm
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• DNA Topoisomerases, Type II
• DNA-Binding Proteins (antagonists & inhibitors)
• Drug Resistance, Neoplasm
• Enzyme Activation (drug effects)
• Humans
• K562 Cells
• Podophyllotoxin (analogs & derivatives, chemistry, pharmacology)
• Topoisomerase II Inhibitors (chemistry, pharmacology)