Melatonin suppresses migration and invasion via inhibition of oxidative stress pathway in glioma cells

Authors

  • Juntao Wang,

    1. Department of Neurosurgery, Qi Lu Hospital, Shandong University, Jinan, China
    Search for more papers by this author
  • Hongbo Hao,

    1. Department of General Surgery, Provincial Hospital affiliated to Shandong University, Jinan, China
    Search for more papers by this author
  • Linli Yao,

    1. Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Histology and Embryology, Shandong University School of Medicine, Jinan, China
    Search for more papers by this author
  • Xiaodan Zhang,

    1. Department of Traditional Chinese Integrated Western Medicine, Qi Lu Hospital, Shandong University, Jinan, China
    Search for more papers by this author
  • Shidou Zhao,

    1. Center for Reproductive Medicine, National Research Center for Assisted Reproductive Technology and Reproductive Genetics, The Key Laboratory for Reproductive Endocrinology of Ministry of Education, Shandong Provincial Key Laboratory of Reproductive Medicine, Shandong University, Jinan, China
    Search for more papers by this author
  • Eng-Ang Ling,

    1. Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
    Search for more papers by this author
  • Aijun Hao,

    1. Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Histology and Embryology, Shandong University School of Medicine, Jinan, China
    Search for more papers by this author
  • Gang Li

    1. Department of Neurosurgery, Qi Lu Hospital, Shandong University, Jinan, China
    Search for more papers by this author

Address reprint requests to Aijun Hao, PhD, Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Histology and Embryology, Shandong University School of Medicine, 44#, Wenhua Xi Road, 250012, Jinan, China.
E-mail: aijunhao@sdu.edu.cn
Gang Li, MD, PhD, Department of Neurosurgery, Qi Lu Hospital, Shandong University, 107#, Wenhua Xi Road, Jinan 250012, China.
E-mail: doctorligang@126.com

Abstract

Abstract:  Melatonin, an indolamine produced and secreted predominately by the pineal gland, exhibits a variety of physiological functions, possesses antioxidant and antitumor properties. In this study, we have shown that pharmacologic concentration (1 mm) of melatonin significantly reduced cell migration and invasion of T98G and U251 glioma cells after 24-hr treatment and inhibited expression of matrix metalloproteinase 2 (MMP 2) and MMP 9. The melatonin inhibition of cell migration and invasion was associated with its reduction of intracellular basal free radical generation. Melatonin at pharmacologic concentration also inhibited the constitutive activation of the reactive oxygen species downstream transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Furthermore, pyrrolidine dithiocarbamate, a NF-κB-specific inhibitor, at 10 μm displayed anti-migration and invasion effects and inhibition of MMP 2 and MMP 9 expression resembling that of melatonin. Taken together, it is concluded that inhibition of migration and invasion of glioma cells by melatonin is associated with the latter in its inhibition of oxidative stress pathway. This suggests a potential therapeutic application of melatonin in the treatment of glioma.

Ancillary