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International Journal Of Bilogical Sciences

.: Home > International Journal Of Bilogical Sciences > 2014 > Volume 10 Number 5 > Antonietta Notaro1, Selenia Sabella1, Ornella Pellerito2, Riccardo Di Fiore1, Anna De Blasio1, Renza Vento1, Giuseppe Calvaruso1* and Michela Giuliano1*

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

Antonietta Notaro1, Selenia Sabella1, Ornella Pellerito2, Riccardo Di Fiore1, Anna De Blasio1, Renza Vento1, Giuseppe Calvaruso1* and Michela Giuliano1*
1. Laboratory of Biochemistry, Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, Polyclinic, Palermo, Italy. 2. Laboratory of Cellular and Developmental Genetics, Department of Molecular Biology, Medical Biochemistry and Pathology, Faculty of Medicine, Université Laval, Québec, Canada. * The authors share senior coauthorship.  Corresponding author: Prof. Michela Giuliano, tel +39-91-6552473, fax +39-91-6552449; Email michela.giuliano@unipa.it.
Abstract :

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.

Keywords :
Cannabinoids, ER stress, autophagy, TRAIL, osteosarcoma cells, GRP78/PAR-4 complex.

Date Deposited : 09 Feb 2016 10:21

Last Modified : 09 Feb 2016 10:21

Official URL: http://www.ijbs.com/v10i5

Volume 10, Number 5, - 2014 , ISSN 1449-2288

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