Synergistic Induction of Apoptosis by Methylseleninic Acid and Cisplatin, The Role of ROS-ERK/AKT-p53 Pathway
Publication in refereed journal


Times Cited
Web of Science26WOS source URL (as at 23/09/2020) Click here for the latest count
Altmetrics Information
.

Other information
AbstractCisplatin-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.
All Author(s) ListZhang YB, Zheng SY, Zheng JS, Wong KH, Huang Z, Ngai SM, Zheng WJ, Wong YS, Chen TF
Journal nameMolecular Pharmaceutics
Detailed descriptiondoi: 10.1021/mp400749f.
Year2014
Month4
Day1
Volume Number11
Issue Number4
PublisherAMER CHEMICAL SOC
Pages1282 - 1293
ISSN1543-8384
LanguagesEnglish-United Kingdom
Keywordsapoptosis; cisplatin; methylseleninic acid; ROS; synergetic effects
Web of Science Subject CategoriesMedicine, Research & Experimental; Pharmacology & Pharmacy; PHARMACOLOGY & PHARMACY; Research & Experimental Medicine

Last updated on 2020-24-09 at 00:45