title: 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.
authors.affiliation: Departamento de Morfología y Biología Celular, Facultad de Medicina de la Universidad de Oviedo, Oviedo, Spain.
authors.forename: Vanesa
authors.initials: V
authors.lastname: Martín
authors.forename: Federico
authors.initials: F
authors.lastname: Herrera
authors.forename: Guillermo
authors.initials: G
authors.lastname: García-Santos
authors.forename: Isaac
authors.initials: I
authors.lastname: Antolín
authors.forename: Jezabel
authors.initials: J
authors.lastname: Rodriguez-Blanco
authors.forename: María
authors.initials: M
authors.lastname: Medina
authors.forename: Carmen
authors.initials: C
authors.lastname: Rodriguez
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D005910:Glioma / Q000378:metabolism*; D008550:Melatonin / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats