0000000000698259
AUTHOR
O Pellerito
p8 (candidate of metasiasis 1) drives ER-stress/autophagy/apoptosis axis induced by the synthetic cannabinoid WIN in HCC cells.
Background: Today, evidence is emerging for the role of autophagy in the regulation of life and death of tumour cells and its relationship with ER-stress signaling. Our previous results demonstrated that hepatoma HepG2 cells are sensitive to apoptotic effects induced by WIN, a synthetic cannabinoid, which acts through a mechanism involving the reduction in the levels of some survival factors and the activation of pro-apoptotic ones. Since WIN effects were observed after 36−48 hours of treatment, we investigated the possible activation of ER-stress and autophagic process in the first hours of WIN treatment focusing our attention on p8, a factor whose expression is upregulated in response to …
The synthetic cannabinoid WIN sensitizes hepatocellular carcinoma cells to TRAIL-induced apoptosis by activating p8/CHOP/DR5 axis.
In this paper we demonstrate that the synthetic cannabinoid WIN sensitizes human hepatocellular carcinoma (HCC) cells to apoptosis mediated by TNF-related apoptosis inducing ligand (TRAIL). The apoptotic mechanism induced by treatment with WIN/TRAIL combination involved the loss of the mitochondrial transmembrane potential and led to the activation of caspases. In HCC cells WIN treatment induced up-regulation of TRAIL death receptor DR5, an effect which seemed to be related to the increase in the level of p8 and CHOP, two factors implicated in cellular stress response and apoptosis. This relationship was suggested by the observation that the down-regulation of p8 or CHOP by specific siRNAs …
Cannabinoid-associated cell death mechanisms in tumor models (review)
In recent years, cannabinoids (the active components of Cannabis sativa) and their derivatives have received considerable interest due to findings that they can affect the viability and invasiveness of a variety of different cancer cells. Moreover, in addition to their inhibitory effects on tumor growth and migration, angiogenesis and metastasis, the ability of these compounds to induce different pathways of cell death has been highlighted. Here, we review the most recent results generating interest in the field of death mechanisms induced by cannabinoids in cancer cells. In particular, we analyze the pathways triggered by cannabinoids to induce apoptosis or autophagy and investigate the in…