Synergistic induction of apoptosis by methylseleninic acid and cisplatin, the role of ROS-ERK/AKT-p53 pathway

Yibo Zhang, Shanyuan Zheng, Jun Sheng Zheng, Ka Hing Wong, Zhi Huang, Sai Ming Ngai, Wenjie Zheng, Yum Shing Wong, Tianfeng Chen

Research output: Journal article publicationJournal articleAcademic researchpeer-review

35 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1282-1293
Number of pages12
JournalMolecular Pharmaceutics
Volume11
Issue number4
DOIs
Publication statusPublished - 7 Apr 2014

Keywords

  • apoptosis
  • cisplatin
  • methylseleninic acid
  • ROS
  • synergetic effects

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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