News Story: Full Text
Sponsored By
Cleveland Clinic Brain Tumor and Neuro-Oncology Center
Please Click On The Above Banner For More Details
Braintumor Website

 

Intracellular signaling pathways involved in the cell growth inhibition of glioma cells by melatonin.


Posted on: 01/25/2006

Intracellular signaling pathways involved in the cell growth inhibition of glioma cells by melatonin.

Cancer Res. 2006 Jan 15;66(2):1081-8.

Martin V, Herrera F, Carrera-Gonzalez P, Garcia-Santos G, Antolin I, Rodriguez-Blanco J, Rodriguez C.

Departamento de Morfologia y Biologia Celular and Instituto Universitario de Oncologia del Principado de Asturias, Facultad de Medicina de la Universidad de Oviedo, Oviedo, Spain.

Melatonin is an indolamine mostly produced in the pineal gland, soluble in water, and highly lipophilic, which allows it to readily cross the blood-brain barrier. Melatonin possesses antioxidant properties and its long-term administration in rodents has not been found to cause noteworthy side effects. In the present work, we found that millimolar concentrations of this indolamine reduced cell growth of C6 glioma cells by 70% after 72 hours of treatment, inhibiting cell progression from G(1) to S phase of the cell cycle. Intraperitoneal administration of 15 mg/kg body weight of melatonin to rats previously injected in the flank with C6 glioma cells reduces tumor growth by 50% 2 weeks after the implant. Inhibition of cell growth does not depend on melatonin membrane receptor activation whereas it seemingly relates to the reduction of intracellular basal free radical levels by 30%. Increase of basal redox state of the cells and constitutive activation of tyrosine kinase receptor [receptor tyrosine kinase (RTK)] pathways, including the extracellular signal-regulated kinase 1/2 (ERK1/2) and the Akt and protein kinase C (PKC) signaling pathways, contribute to the progression of the gliomas leading to the constitutive activation of the redox-dependent survival transcription factor nuclear factor kappaB (NF-kappaB). The antioxidant effect of melatonin in C6 cells is associated to inhibition of NF-kappaB and Akt, but not of ERK1/2. The antiproliferative effect of the indolamine on these cells is partially abolished when coincubated with the PKC activator 12-O-tetradecanoylphorbol-13-acetate, thus indicating that the ability of melatonin to change cellular redox state may be inactivating the pathway RTK/PKC/Akt/NF-kappaB. (Cancer Res 2006; 66(2): 1081-8).

PMID: 16424044 [PubMed - in process]


Click HERE to return to brain tumor news headlines


Home | Brain Tumor Guide | FAQs | Find A Treatment
Noteworthy Treatments | News | Virtual Trial | Videos | Novocure Optune® | Newsletter
Donations | Brain Tumor Centers | Survivor Stories | Temodar®
Fundraising For Research | Unsubscribe | Contact Us

Copyright (c) 1993 - 2019 by:
The Musella Foundation For Brain Tumor Research & Information, Inc
1100 Peninsula Blvd
Hewlett, NY 11557
888-295-4740