Involvement of PAR-4 in Cannabinoid-Dependent Sensitization of Osteosarcoma Cells to TRAIL-Induced Apoptosis

6533b85efe1ef96bd12c09f1

RESEARCH PRODUCT

Involvement of PAR-4 in Cannabinoid-Dependent Sensitization of Osteosarcoma Cells to TRAIL-Induced Apoptosis

Michela Giuliano Riccardo Di Fiore Ornella Pellerito Giuseppe Calvaruso Antonietta Notaro Renza Vento Selenia Sabella Anna De Blasio

subject

Autophagosome autophagy Programmed cell death Cannabinoids ER stress autophagy TRAIL osteosarcoma cells GRP78/PAR-4 complex.Cannabinoid receptor Morpholines Cell Apoptosis TRAIL Naphthalenes Biology GRP78/PAR-4 complex.Applied Microbiology and Biotechnology TNF-Related Apoptosis-Inducing Ligand Cadaverine Cell Line Tumor Settore BIO/10 - Biochimica medicine Humans RNA Small Interfering Endoplasmic Reticulum Chaperone BiP Molecular Biology Heat-Shock Proteins Ecology Evolution Behavior and Systematics Cell Proliferation Cannabinoid Receptor Agonists Osteosarcoma Cannabinoids Autophagy Cell Cycle Checkpoints osteosarcoma cells Cell Biology Cell cycle Endoplasmic Reticulum Stress Acridine Orange Benzoxazines Cell biology medicine.anatomical_structure Apoptosis Autophagosome membrane Apoptosis Regulatory Proteins ER stress Microtubule-Associated Proteins Research Paper Developmental Biology

description

The synthetic cannabinoid WIN 55,212-2 is a potent cannabinoid receptor agonist with anticancer potential. Experiments were performed to determine the effects of WIN on proliferation, cell cycle distribution, and programmed cell death in human osteosarcoma MG63 and Saos-2 cells. Results show that WIN induced G2/M cell cycle arrest, which was associated with the induction of the main markers of ER stress (GRP78, CHOP and TRB3). In treated cells we also observed the conversion of the cytosolic form of the autophagosome marker LC3-I into LC3-II (the lipidated form located on the autophagosome membrane) and the enhanced incorporation of monodansylcadaverine and acridine orange, two markers of the autophagic compartments such as autolysosomes. WIN also induced morphological effects in MG63 cells consisting in an increase in cell size and a marked cytoplasmic vacuolization. However, WIN effects were not associated with a canonical apoptotic pathway, as demonstrated by the absence of specific features, and only the addition of TRAIL to WIN-treated cells led to apoptotic death probably mediated by up-regulation of the tumor suppressor factor PAR-4, whose levels increased after WIN treatment, and by the translocation of GRP78 on cell surface.

year	journal	country	edition	language
2014-01-01

10.7150/ijbs.8337 http://hdl.handle.net/10447/93445