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Involvement of protein kinase C in melatonin’s oncostatic effect in C6 glioma cells
Author(s) -
Martín Vanesa,
Herrera Federico,
GarcíaSantos Guillermo,
Antolín Isaac,
RodriguezBlanco Jezabel,
Medina María,
Rodriguez Carmen
Publication year - 2007
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2007.00468.x
Subject(s) - melatonin , protein kinase c , protein kinase b , intracellular , biology , glioma , effector , signal transduction , cancer research , microbiology and biotechnology , endocrinology
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)‐κB. 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‐κB 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‐κB activity inhibition and modulation of cell cycle‐related gene expression.