Involvement of protein kinase C in melatonin's oncostatic effect in C6 glioma cells.

Abstract:

:Classical anticancer therapies often are ineffective in patients with malignant glioma who have a survival of <1 year. Our previous studies showed a potent inhibitory effect of melatonin on glioma cell proliferation. This effect seems to be mediated by the well-known antioxidant properties of this molecule and the negative regulation of some intracellular effectors, such as the kinase Akt or the transcription factor nuclear factor (NF)-kappaB. Finally, protein kinase C (PKC) also seems to be implicated in this effect although the intracellular pathways involved have not been elucidated. In this study, we analyzed the role of PKC in the regulation by melatonin of intracellular effectors leading to inhibition of cell proliferation. Activation of PKC by incubation with triphorbol ester acetate (TPA) blocks the inhibitory effect of melatonin on Akt and NF-kappaB activity. Moreover, incubation with melatonin induces a decrease in p21 expression in these cells that is partially blocked by co-incubation with TPA. Taken together, these results suggest that melatonin's oncostatic effect on glioma cells is mediated, at least in part, by the inhibition of PKC activity which, in turn, results in Akt and NF-kappaB activity inhibition and modulation of cell cycle-related gene expression.

journal_name

J Pineal Res

authors

Martín V,Herrera F,García-Santos G,Antolín I,Rodriguez-Blanco J,Medina M,Rodriguez C

doi

10.1111/j.1600-079X.2007.00468.x

subject

Has Abstract

pub_date

2007-10-01 00:00:00

pages

239-44

issue

3

eissn

0742-3098

issn

1600-079X

pii

JPI468

journal_volume

43

pub_type

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