title: Synergistic induction of apoptosis by methylseleninic acid and cisplatin, the role of ROS-ERK/AKT-p53 pathway.
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.
authors.affiliation: Department of Chemistry, Jinan University , Guangzhou 510632, China.
authors.forename: Yibo
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shanyuan
authors.initials: S
authors.lastname: Zheng
authors.forename: Jun-Sheng
authors.initials: JS
authors.lastname: Zheng
authors.forename: Ka-Hing
authors.initials: KH
authors.lastname: Wong
authors.forename: Zhi
authors.initials: Z
authors.lastname: Huang
authors.forename: Sai-Ming
authors.initials: SM
authors.lastname: Ngai
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zheng
authors.forename: Yum-Shing
authors.initials: YS
authors.lastname: Wong
authors.forename: Tianfeng
authors.initials: T
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D004357:Drug Synergism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D006801:Humans; D016566:Organoselenium Compounds / Q000494:pharmacology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: D000970:Antineoplastic Agents; D016566:Organoselenium Compounds; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; C008493:methylselenic acid; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D002945:Cisplatin