Synergistic Induction of Apoptosis by Methylseleninic Acid and Cisplatin, The Role of ROS-ERK/AKT-p53 Pathway
| Autor: | Yum Shing Wong, Shanyuan Zheng, Keith Kwong Hon Wong, Tianfeng Chen, Jun Sheng Zheng, Sai-Ming Ngai, Yibo Zhang, Zhi Huang, Wenjie Zheng |
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| Rok vydání: | 2014 |
| Předmět: |
MAPK/ERK pathway
Chemosensitizer Pharmaceutical Science Antineoplastic Agents Apoptosis medicine.disease_cause Cell Line Tumor Organoselenium Compounds Drug Discovery medicine Humans Phosphorylation Extracellular Signal-Regulated MAP Kinases Protein kinase B Cisplatin Chemistry Drug Synergism Cancer cell Cancer research Molecular Medicine Tumor Suppressor Protein p53 Signal transduction Reactive Oxygen Species Proto-Oncogene Proteins c-akt Oxidative stress Signal Transduction medicine.drug |
| Zdroj: | Molecular Pharmaceutics. 11:1282-1293 |
| ISSN: | 1543-8392 1543-8384 |
| DOI: | 10.1021/mp400749f |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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