A novel pyrazolone-based derivative induces apoptosis in human esophageal cells via reactive oxygen species (ROS) generation and caspase-dependent mitochondria-mediated pathway.

Abstract

Pyrazolone complexes have strong bio-activity but the anti-tumor mechanism of pyrazolone-based metal complexes is not fully understood. In this study, the inhibitory effect and possible mechanism of a novel pyrazolone-based derivative compound (Cd-PMPP-SAL) on human esophageal cancer cells were investigated. We found that Cd-PMPP-SAL inhibited the proliferation of Eca-109 cells in a dose-dependent manner and induced the apoptosis in the cells. Interestingly, Cd-PMPP-SAL promoted the production of ROS, loss of mitochondrial membrane potential, PARP cleavage and activation of caspase-3/9. These results suggest Cd-PMPP-SAL-induced apoptosis might be mediated by the increased production of ROS and caspase-dependent mitochondria-mediated pathway. These results suggest that Cd-PMPP-SAL is a potential candidate for the treatment of esophageal cancer.

• Authors: Jing Zhao, Li Zhang, Jinyao Li, Ting Wu, Meifang Wang, Guancheng Xu, Fuchun Zhang, Lang Liu, Jianhua Yang, Surong Sun
• Journal: Chemico-biological interactions (Chem Biol Interact) Vol. 231 Pg. 1-9 (Apr 25 2015) ISSN: 1872-7786 [Electronic] Ireland
• PMID: 25684395 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Pyrazolones
• Reactive Oxygen Species
• Cadmium
• pyrazolone
• Caspases

Topics

• Antineoplastic Agents (chemistry, pharmacology)
• Apoptosis (drug effects)
• Cadmium (chemistry, pharmacology)
• Caspases (metabolism)
• Cell Line, Tumor
• Esophageal Neoplasms (drug therapy, metabolism, pathology)
• Esophagus (drug effects, metabolism, pathology)
• Humans
• Mitochondria (drug effects, metabolism)
• Pyrazolones (chemistry, pharmacology)
• Reactive Oxygen Species (metabolism)
• Signal Transduction