Bis(acetylacetonato)-oxidovanadium(IV) and sodium metavanadate inhibit cell proliferation via ROS-induced sustained MAPK/ERK activation but with elevated AKT activity in human pancreatic cancer AsPC-1 cells

详细信息    查看全文

• 作者：Jing-Xuan Wu ; Yi-Hua Hong ; Xiao-Gai Yang
• 关键词：Vanadium compounds ; Reactive oxygen species ; Extracellular signal ; regulated protein kinase ; PI3K/AKT signaling pathway ; AsPC ; 1 cells
• 刊名：Journal of Biological Inorganic Chemistry
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：21
• 期：8
• 页码：919-929
• 全文大小：3,144 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Biochemistry
  Microbiology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-1327
• 卷排序：21

文摘

In this study, the antiproliferative effect of bis(acetylacetonato)-oxidovanadium(IV) and sodium metavanadate and the underlying mechanisms were investigated in human pancreatic cancer cell line AsPC-1. The results showed that both exhibited an antiproliferative effect through inducing G2/M cell cycle arrest and can also cause elevation of reactive oxygen species (ROS) levels in cells. Moreover, the two vanadium compounds induced the activation of both PI3K/AKT and MAPK/ERK signaling pathways dose- and time-dependently, which could be counteracted with the antioxidant N-acetylcysteine. In the presence of MEK-1 inhibitor, the degradation of Cdc25C, inactivation of Cdc2 and accumulation of p21 were relieved. However, the treatment of AKT inhibitor did not cause any significant effect. Therefore, it demonstrated that the ROS-induced sustained MAPK/ERK activation rather than AKT contributed to vanadium compounds-induced G2/M cell cycle arrest. The current results also exhibited that the two vanadium compounds did not induce a sustained increase of ROS generation, but the level of ROS reached a plateau instead. The results revealed that an intracellular feedback loop may be against the elevated ROS level induced by vanadate or VO(acac)₂, evidenced by the increased GSH content, the unchanged level at the expression of antioxidant enzymes. Therefore, vanadium compounds can be regarded as a novel type of anticancer drugs through the prolonged activation of MAPK/ERK pathway but retained AKT activity. The present results provided a proof-of-concept evidence that vanadium-based compounds may have the potential as both antidiabetic and antipancreatic cancer agents to prevent or treat patients suffering from both diseases.