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

香港中文大學研究人員

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摘要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.
著者Zhang YB, Zheng SY, Zheng JS, Wong KH, Huang Z, Ngai SM, Zheng WJ, Wong YS, Chen TF
期刊名稱Molecular Pharmaceutics
詳細描述doi: 10.1021/mp400749f.
出版年份2014
月份4
日期1
卷號11
期次4
出版社AMER CHEMICAL SOC
頁次1282 - 1293
國際標準期刊號1543-8384
語言英式英語
關鍵詞apoptosis; cisplatin; methylseleninic acid; ROS; synergetic effects
Web of Science 學科類別Medicine, Research & Experimental; Pharmacology & Pharmacy; PHARMACOLOGY & PHARMACY; Research & Experimental Medicine

上次更新時間 2020-24-10 於 02:01