Melatonin sensitizes human malignant glioma cells against TRAIL-induced cell death

Melatonin enhances the anti-tumor effect of sorafenib via AKT/p27-mediated cell cycle arrest in hepatocarcinoma cell lines

“…47,48 Indeed, MT can enhance the activity of many chemotherapeutic agents allowing the use of lower doses of these agents and thus reducing their side effects. 49,50 In this study, we demonstrated not only the combined antitumor effects of MT and sorafenib against HCC in vitro, but also a novel mechanism by which MT sensitized HCC cells to sorafenib. In addition, our study evaluated the anticancer activity of MT-sorafenib combined treatment on tumor growth in There are four phases in the eukaryotic cell cycle.…”

“…Vanesa Martín and colleagues showed that MT inhibits AKT activity in human glioma cells without modifying MAPKs (ERK, p38, and JNK) activity. 50 Bo Zhai et al showed that inhibition of AKT reversed the acquired resistance to sorafenib. 65 Therefore, we next questioned whether p-AKT could regulate p27 via c-myc, and thus affecting cell cycle progression.…”

Molecular aspects of melatonin (MLT)-mediated therapeutic effects

“…RAMOS-1 human leukaemic cells when treated with MLT resulted in the release of mitochondrial cytochrome-c followed by the down-regulation of Bcl-2 gene product, which indicated the activation of apoptosis pathways (Trubiani et al, 2005). Dose Interestingly, extrinsic pathways of apoptotic cell death via TNF-related apoptosis-inducing ligand (TNF/TRAIL) signal transduction have been found to be initiated by MLT in human glioma cells (Martin et al, 2010). In a variety of haematological cancer cells, MLT was found to enhance reactive oxygen species (ROS) production followed by depolarizing the MLT not only stimulates dephosphorylation and nuclear import of histone deacetylase 4 (HDAC4) but also decreases H3 acetylation, which resulted in the down-regulation of bcl-2 expression.…”

Modulation of tumor necrosis factor related apoptosis-inducing ligand (TRAIL) receptors in a human osteoclast model in vitro

“…Further linking of TRAIL to Akt is evidenced by a study by Nam et al in 2003linking Akt to increased FLIP production (Nam et al, 2003. One possible mechanism for TRAIL-induced Akt reduction would be to follow closely that of TNF-a; modulating PKC activity via the TRAIL receptor (Martin et al, 2010). If the mechanism is similar to that of TNF-a; this as yet un-established signaling pathway might work by binding the TRADD complex at the intracellular DD of the receptor, recruiting TRAF and subsequently p62, leading to a modulation of PKC activity, thereby decreasing Akt activation.…”

“…The effect could to be induced by a modulation of PKC activity (similar to that in TNF alpha) which in turn decreases Akt activation leading to an increase in TRAIL-R2 (DR5) levels and a decrease in the antiapoptotic proteins survivin and bcl-2 levels. (Adapted in part from Martin V et al 2010) Modulation of its receptors by TRAIL could represent an autocrine positivefeedback control, carried out between protein production and surface transport and expression. These results suggest that with repeated or prolonged TRAIL stimulation, the osteoclast has a built in control in the case that it proves initially incapable to undergo apoptosis.…”