Apoptosis induced in HepG2 cells by the synthetic cannabinoid WIN: involvement of the transcription factor PPARgamma.

2008

It has recently been shown that cannabinoids induce growth inhibition and apoptosis in different tumour cell lines. In the current study, the effects of WIN 55,212-2 (WIN), a synthetic and potent cannabinoid receptor agonist, are investigated in hepatoma HepG2 cells and a possible signal transduction pathway is proposed. In these cells, WIN induces a clear apoptotic effect which was accompanied by up-regulation of the death-signalling factors Bax, Bcl-X(S), t-Bid and down-regulation of the survival factors survivin, phospho-AKT, Hsp72 and Bcl-2. Moreover, WIN-induced apoptosis is associated with JNK/p38 MAPK pathway activation and mitochondrial depolarisation demonstrated by a cytofluorimet…

WIN induces apoptotic cell death in human colon cancer cells through a block of autophagic flux dependent on PPARγ down-regulation.

2014

Cannabinoids have been reported to possess anti-tumorigenic activity in cancer models although their mechanism of action is not well understood. Here, we show that the synthetic cannabinoid WIN55,212-2 (WIN)-induced apoptosis in colon cancer cell lines is accompanied by endoplasmic reticulum stress induction. The formation of acidic vacuoles and the increase in LC3-II protein indicated the involvement of autophagic process which seemed to play a pro-survival role against the cytotoxic effects of the drug. However, the enhanced lysosomal membrane permeabilization (LMP) blocked the autophagic flux after the formation of autophagosomes as demonstrated by the accumulation of p62 and LC3, two ma…

140 p8 (Candidate Of Metastasis 1) drives ER-stress/autophagy/apoptosis axis induced by the synthetic cannabinoid WIN in HCC cells

2010

Diorganotin(IV) N-acetyl-L-cysteinate complexes: synthesis, solid state, solution phase, DFT and biological investigations.

2009

Diorganotin(IV) complexes of N-acetyl-L-cysteine (H(2)NAC; (R)-2-acetamido-3-sulfanylpropanoic acid) have been synthesized and their solid and solution-phase structural configurations investigated by FTIR, Mössbauer, (1)H, (13)C and (119)Sn NMR spectroscopy. FTIR results suggested that in R(2)Sn(IV)NAC (R = Me, Bu, Ph) complexes NAC(2-) behaves as dianionic tridentate ligand coordinating the tin(IV) atom, through ester-type carboxylate, acetate carbonyl oxygen atom and the deprotonated thiolate group. From (119)Sn Mössbauer spectroscopy it could be inferred that the tin atom is pentacoordinated, with equatorial R(2)Sn(IV) trigonal bipyramidal configuration. In DMSO-d(6) solution, NMR spectr…

Cannabinoid-associated cell death mechanisms in tumor models

2012

In recent years, cannabinoids (the active compo- nents 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 …

Hsp72 controls bortezomib-induced HepG2 cell death via interaction with pro-apoptotic factors.

2007

The proteasome inhibitor bortezomib is an efficacious inducer of apoptosis in the hepatoma HepG2 cell line. This study shows that bortezomib increased in these cells the level of the survival factor Hsp72 in a time- and dose-dependent manner. In a first phase of treatment, Hsp72 rapidly increased so that at 24 h of incubation with 50 nM bortezomib its level was approximately five-fold higher than the control. In this phase Hsp72 seemed to play a role in preventing HepG2 cell death, since it interacted with and sequestered the pro-apoptotic factors p53, AIF, Bax and Apaf-1. During a second day of treatment, although the nuclear levels of Hsp72, p53 and AIF increased, the interaction of Hsp72…

Notch inhibition restores TRAIL-mediated apoptosis via AP1-dependent upregulation of DR4 and DR5 TRAIL receptors in MDA-MB-231 breast cancer cells.

2013

Notch is a family of transmembrane receptors whose activation through proteolytic cleavage by γ-secretase targets genes which participate in cell development, differentiation and tumorigenesis. Notch signaling is constitutively activated in various cancers, including breast cancer and its upregulation is usually related with poor clinical outcomes. Therefore, targeting Notch signaling with γ-secretase inhibitors (GSIs) is considered a promising strategy for cancer treatment. We report that the γ-secretase inhibitor-I (GSI-I) sensitizes human breast cancer cells to apoptosis mediated by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). The antiproliferative GSI-I/TRAIL synergi…

The role of oxidative stress in apoptosis induced by the histone deacetylase inhibitor suberoylanilide hydroxamic acid in human colon adenocarcinoma …

2008

Histone deacetylase inhibitors (HDACIs) activate genes that promote cell cycle arrest and apoptosis in a number of tumor cells. This study showed that suberoylanilide hydroxamic acid (SAHA), a potent and commonly used HDACI, induced apoptosis in human colon adenocarcinoma HT-29 cells in a time- and dose-dependent manner. This effect was accompanied by the induction of oxidative stress, dissipation of mitochondrial transmembrane potential and activation of executioner caspases. Moreover, SAHA increased the levels of phosphorylated active forms of p38 and JNK. The addition of either the antioxidant N-acetylcysteine or the specific inhibitor of NADPH oxidase diphenylene iodonium chloride reduc…

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

2014

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 t…

Anandamide-induced apoptosis in Chang liver cells involves ceramide and JNK/AP-1 pathway

2006

In the present study we demonstrate that anandamide, the most important endogenous cannabinoid, markedly induced apoptosis in Chang liver cells, an immortalized non-tumor cell line derived from normal liver tissue, while it induced only modest effects in a number of hepatoma cell lines. The apoptotic effect was reduced by methyl-beta-cyclodextrin, a membrane cholesterol depletor, suggesting an interaction between anandamide and the membrane microdomains named lipid rafts. Anandamide effects were mediated by the production of ceramide, as demonstrated by experiments performed with the sphingomyelinase inhibitor, desipramine, or with the sphingomyelinase activator, melittin. This conclusion w…

The Synthetic Cannabinoid WIN 55,212-2 Sensitizes Hepatocellular Carcinoma Cells to Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)-I…

2010

In this article, we demonstrate that the synthetic cannabinoid R-(+)-(2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrol[1,2,3-de]-1,4-benzoxazin-6-yl)-(1-naphthalenyl) methanone mesylate (WIN 55,212-2) sensitizes human hepatocellular carcinoma (HCC) cells to apoptosis mediated by tumor necrosis-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 the up-regulation of TRAIL death receptor DR5, an effect that seemed to be related to the increase in the level of p8 and CHOP, two factors implicat…

Synthesis, chemical characterization and biological activity of new histone acetylation/deacetylation specific inhibitors: a novel and potential appr…

2013

Three new triorganotin(IV) complexes of valproic acid (vp1, Me3Sn-valproate; vp2, Bu3Sn-valproate; vp3, Ph3Sn-valproate) have been synthesized and investigated by spectroscopic and biological methods. An anionic, monodentate valproate ligand was observed, ester-like coordinating the tin atom on a tetra-coordinated, monomeric environment. The structures, though, can distort towards a penta-coordination, as a consequence of a long range O center dot center dot center dot Sn interaction. Crystallographic and NMR findings confirm this situation both in solid state and solution. Biological finding evidenced a clear cytotoxic action of the complexes in hepatocellular carcinoma cell cultures: one …

Factors that protect HepG2 cells by anandamide-induced cell death

2006

Role of PPARγ in apoptosis induced by cannabinoids in hepatoma HepG2 cells.

2007

The synthetic cannabinoid WIN55,212-2 synergizes with the death receptor ligand TRAIL to induce apoptotic effect in HepG2 hepatoma cells.

2008

Different expression of PPARs in WIN-treated cells: the game of roles

2012

USO TERAPEUTICO COMBINATO DI ORGANOSTAGNO(IV) ED INIBITORI DELLE DEACETILASI ISTONICHE

2010

Bu2Sn(N-acetyl-L-cysteinate) antitumor activity on HepG2 cells

2010

ORGANOSTAGNO(IV) COMPLESSI CON N-ACETILCISTEINA AD ATTIVITÀ ANTITUMORALE, PROCEDIMENTO PER LA LORO PRODUZIONE E LORO USO.

2008

The cannabinoid WIN induces DR5 receptor expression in hepatoma cells sensitizing them to TRAIL signal

2009

Synergistic effects induced by combinations of the synthetic cannabinoid WIN55,212-2 and the death receptor ligand TRAIL in hepatoma HepG2 cells.

2008

Hsp-72 contrasta l'effetto apoptotico indotto dal bortezomib in cellule di epatoblastoma umano Hep-G2

2006

Synthesis, structural investigation and biological activity of metal ions complexes of N-acetylcysteine and carbocysteine

2006

Complessi di nuova sintesi di derivati della cisteina con ioni metallici

2006

Autophagy and ER-stress participate to cannabinoid-induced apoptosis in colon carcinoma cells

2012

A comparison between the role of SPARC in osteogenic differentiation of mesenchymal stem cells and in WIN/TRAIL-induced apoptosis in osteosarcoma cel…

2012

Degradation of IkBalfa during apoptosis induced by proteasome inhibitors in hepatoma cells.

2004

COINVOLGIMENTO DELLO STRESS DEL RETICOLO E DEL PROCESSO AUTOFAGICO NELL’APOPTOSI INDOTTA DAL CANNABINOIDE SINTETICO WIN IN CELLULE DI EPATOMA UMANO I…

2009

Studi da noi condotti precedentemente hanno dimostrato la capacità del cannabinoide sintetico WIN di indurre apoptosi in cellule di epatocarcinoma umano HepG2 attraverso un meccanismo, dipendente dal fattore trascrizionale PPARg, che prevede riduzione dei livelli di alcuni fattori di sopravvivenza e attivazione di fattori pro-apoptotici della famiglia Bcl-2 (M. Giuliano et al. Biochimie. 2009). Recentemente è, inoltre, emerso che in cellule di glioma i cannabinoidi possono stimolare l’apoptosi attraverso induzione di stress del reticolo endoplasmatico seguito da autofagia. Scopo L'obiettivo del presente studio è stato quello di valutare il coinvolgimento dell’autofagia nel percorso di morte…

WIN55,212-2, a synthetic agonist of cannabinoid receptors, sensitizes tumor cells to TRAIL-induced apoptosis.

2007

THE CANNABINOID AGONIST WIN55,212-2 INDUCES APOPTOSIS IN HUMAN HEPATOMA CELLS.

2006

APOPTOTIC EFFECTS INDUCED BY ANANDAMIDE IN HEPATIC CELLS.

2005

TWO-DIMENSIONAL ANALYSIS OF PROTEIN EXPRESSION PATTERNS

2008

The transcription factor CHOP is critical for WIN-mediated DR5 up-regulation in apoptosis induced by WIN/TRAIL co-treatment in hepatoma cells

2009

New histone acetylation/deacetylation specific inhibitors: a novel and potential approach to cancer therapy

2011

The acetylation status of histones is regulated in eukaryotes by two kinds of enzymes, histone acetyltransferases (HATs) and histone deacetylases (HDACs), which are responsible for acetylation and deacetylation of lysines residues in N-terminal tails of histone.[1] Thus acetylation, together with phosphorylation and methylation of N-terminal tail of histones, are involved in regulating fundamental processes, such as proliferation and cell death.[2-3] Sodium butyrate, which belongs together with valproic acid to the class of short chain fatty acids, was the first HDAC inhibitor (HDACI) to be identified.[1] Organotin compounds have various influences on physical function including the hormone…

CCDC 830010: Experimental Crystal Structure Determination

2013

Related Article: Ornella Pellerito, Cristina Prinzivalli, Elisabetta Foresti, Piera Sabatino, Michele Abbate, Girolamo Casella, Tiziana Fiore, Michelangelo Scopelliti, Claudia Pellerito, Michela Giuliano, Giulia Grasso, Lorenzo Pellerito|2013|J.Inorg.Biochem.|125|16|doi:10.1016/j.jinorgbio.2013.04.008