Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/34909
Title: Synergistic induction of apoptosis by methylseleninic acid and cisplatin, the role of ROS-ERK/AKT-p53 pathway
Authors: Zhang, Y
Zheng, S
Zheng, JS
Wong, KH 
Huang, Z
Ngai, SM
Zheng, W
Wong, YS
Chen, T
Keywords: Methylseleninic acid
Cisplatin
Apoptosis
Synergetic effects
ROS
Issue Date: 2014
Publisher: American Chemical Society
Source: Molecular pharmaceutics, 2014, v. 11, no. 4, p. 1282-1293 How to cite?
Journal: Molecular pharmaceutics 
Abstract: Cisplatin-based therapy is one of the most important chemotherapy treatments for cancers. However, its efficacy is greatly limited by drug resistance and undesirable side effects. Therefore, it is of great importance to develop chemosensitizing agents to cisplatin. In the present study, we demonstrated the strategy to use methylseleninic acid (MeSe) as a synergistic agent of cisplatin and elucidated their action mechanisms. The combination of MeSe and cisplatin exhibited synergistic anticancer efficacy and achieved greater selectivity between cancer cell and normal cell. By inducing intracellular oxidative stress, MeSe potentiated cisplatin-induced DNA damage and led to enhanced p53 phosphorylation, followed by increased activation of both mitochondrial and death receptor pathway. Down-regulation of phosphorylated AKT and ERK also played important roles in the synergistic effects of MeSe and cisplatin. Our results suggested that the strategy to apply MeSe as a synergistic agent to cisplatin could be a highly efficient way to achieve anticancer synergism by targeting the intracellular redox system. MeSe might be a candidate for clinical application as a chemosensitizer to cisplatin-based therapy for cancer treatments, especially for hepatocellular carcinoma.
URI: http://hdl.handle.net/10397/34909
ISSN: 1543-8384
EISSN: 1543-8392
DOI: 10.1021/mp400749f
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