title: Melatonin suppresses migration and invasion via inhibition of oxidative stress pathway in glioma cells.
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 (1mm) 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 10μm 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.
authors.affiliation: Department of Neurosurgery, Qi Lu Hospital, Shandong University, Jinan, China.
authors.forename: Juntao
authors.initials: J
authors.lastname: Wang
authors.forename: Hongbo
authors.initials: H
authors.lastname: Hao
authors.forename: Linli
authors.initials: L
authors.lastname: Yao
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Zhang
authors.forename: Shidou
authors.initials: S
authors.lastname: Zhao
authors.forename: Eng-Ang
authors.initials: EA
authors.lastname: Ling
authors.forename: Aijun
authors.initials: A
authors.lastname: Hao
authors.forename: Gang
authors.initials: G
authors.lastname: Li
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D005609:Free Radicals / Q000378:metabolism; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D008550:Melatonin / Q000494:pharmacology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology; D017382:Reactive Oxygen Species; D015398:Signal Transduction / Q000187:drug effects; D013859:Thiocarbamates / Q000494:pharmacology
chemical_list: D005609:Free Radicals; D016328:NF-kappa B; D011759:Pyrrolidines; D017382:Reactive Oxygen Species; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D008550:Melatonin