Melatonin induces apoptosis in C6 glioma cells. Therapeutic Implications.

SAPIENZA, C.E.; ALAIMO A.; GOROJOD R.; KOTLER M.L.

Huerta Grande, Provincia de Córdoba, Argentina

Congreso; I Reunión Conjunta de Neurociencias (IRCN); 2009

Sociedad Argentina de Investigación en Neurociencias

Malignant gliomas are resistant to various proapoptotic therapies, such as radiotherapy and conventional chemotherapy. Melatonin is a hormone synthesized by pineal gland with widespread functions. Several evidences indicate an antiproliferative action of melatonin in tumor cells. However, no definitive intracellular pathway has been described to explain this antineoplasic effect. In this study, we demonstrated that melatonin induces a dose-dependent decrease in cell viability. Melatonin (2mM, 24hs) induced cell cytotoxicity in the presence and absence of FBS, measured by both MTT (18}1%, 57}1%) and Neutral Red (27}4%, 41}2%). Additionaly, cell death was visualized by phase-contrast microscopy as a dramatic disruption of the cell monolayer with retraction of astrocytic processes. In this conditions, caspase 3 activity, a marker of apoptotic cell death, increases 81}23% and 208}40% in the presence and absence of FBS, respectively. A correlation between ERK phosphorylation and p53 levels was detected by Western Blot analysis. Incubations with PD98059 (25ìM), a MEK activity inhibitor, resulted in a total recovery of viability in absence of FBS; however, in the presence of serum, PD98059 enhances melatonin-induced injury. Our results suggest that melatonin may be an important endogenous cell death modulator and a potential therapeutic agent in glial tumors.