Melatonin induces the mitochondrial apoptotic pathway in C6 glioma cells

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

Huerta Grande, Provincia de Córdoba, Argentina

Congreso; II Reunión conjunta Taller Argentino de Neurociencias-Sociedad Argentina de Investigación en Neurociencias; 2010

Sociedad Argentina de Neurociencias

Melatonin (MLT) is an indoleamine synthesized by the pineal gland. In vitro and in vivo experiments have shown that MLT influences mitochondrial homeostasis. Tumor cells present higher levels of ROS and oxidative damage markers than normal cells. In the present work we demonstrated that MLT (2mM, 48hs) induced cell death both in the presence and in the absence of serum, measured by MTT assay (40±4% and 63±5% respectively). Nuclear morphology analysis employing Hoechst 33258 dye showed condensation and DNA fragmentation at 24 and 48hs. Furthermore, we studied the effect of MLT on Bcl-2 family proteins expression. MLT increased Bax expression and decreased Bid proform, in a dose-dependent manner. Bcl-2 and Bcl-xL levels were also investigated. Analysis of mitochondrial integrity employing MitoTracker Red dye showed the occurrence of different morphologies: normal (tubular) mitochondria in controls, and intermediate (partially fragmented) and fragmented mitochondria in MLT-treated cells, in both, the presence or absence of serum. ROS enhancement seems not to be the only event responsible of MLT-induced apoptosis. Our results suggest that MLT is capable of inducing cell death in glioma cells by activating the mitochondrial apoptotic pathway.