Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors

Casanova, Mercedes; Blázquez, Cristina; Martínez-Palacio, Jesús; Villanueva, Concepción; Fernández-Aceñero, M. Jesús; Huffman, John W.; Jorcano, José L.; Guzmán, Manuel

doi:10.1172/jci16116

Cited by 208 publications

(251 citation statements)

References 34 publications

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“…Although this very surprising aspect of cannabinoid action has been already documented in other sets of experiments [39][40][41][42], there is not at the moment a convincing explanation for this behavior. It may be that this dual property depends on differences in the features of normal versus transformed cells.…”

Section: Discussionmentioning

confidence: 77%

The non-psychoactive cannabidiol triggers caspase activation and oxidative stress in human glioma cells

Massi

Vaccani

Bianchessi

et al. 2006

Cell. Mol. Life Sci.

176

156

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Recently, we have shown that the non-psychoactive cannabinoid compound cannabidiol (CBD) induces apoptosis of glioma cells in vitro and tumor regression in vivo. The present study investigated a possible involvement of caspase activation and reactive oxygen species (ROS) induction in the apoptotic effect of CBD. CBD produced a gradual, time-dependent activation of caspase-3, which preceded the appearance of apoptotic death. In addiction, release of cytochrome c and caspase-9 and caspase-8 activation were detected. The exposure to CBD caused in glioma cells an early production of ROS, depletion of intracellular glutathione and increase activity of glutathione reductase and glutathione peroxidase enzymes. Under the same experimental condition, CBD did not impair primary glia. Thus, we found a different sensitivity to the anti-proliferative effect of CBD in human glioma cells and non-transformed cells that appears closely related to a selective ability of CBD in inducing ROS production and caspase activation in tumor cells.

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Section: Discussionmentioning

confidence: 77%

The non-psychoactive cannabidiol triggers caspase activation and oxidative stress in human glioma cells

Massi

Vaccani

Bianchessi

et al. 2006

Cell. Mol. Life Sci.

176

156

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“…CNR2 is the "peripheral" cannabinoid receptor, mostly expressed by cells of the immune system and responsible for mediating the non-psychoactive effects of cannabinoids such as analgesia and immunosuppression [27]. Although relatively little is known about the cannabinoid receptors, CNR2 has evoked medical interest as an inducer of apoptosis, inhibitor of angiogenesis and skin tumour growth [28], and a potent antiinflammatory and immunosuppressive agent. [29].…”

Section: Experimental Validation Of the Microarray Resultsmentioning

confidence: 99%

Critical role of extracellular vesicles in modulating the cellular effects of cytokines

Szabó

Tarr

Pálóczi

et al. 2014

Cell. Mol. Life Sci.

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Under physiological and pathological conditions, extracellular vesicles (EVs) are present in the extracellular compartment simultaneously with soluble mediators. We hypothesized that cytokine effects may be modulated by EVs, the recently recognized conveyors of intercellular messages. In order to test this hypothesis, human monocyte cells were incubated with CCRF acute lymphoblastic leukemia cell line-derived EVs with or without the addition of recombinant human TNF, and global gene expression changes were analysed. EVs alone regulated the expression of numerous genes related to inflammation and signaling. In combination, the effects of EVs and TNF were additive, antagonistic or independent. The differential effects of EVs and TNF or their simultaneous presence were also validated by Taqman assays, ELISA and testing different populations of purified EVs. In the case of the paramount chemokine IL-8, we were able to demonstrate a synergistic up-regulation by purified EVs and TNF. Our data suggest that neglecting the modulating role of EVs on the effects of soluble mediators may skew experimental results. On the other hand, considering the combined effects of cytokines and EVs may prove therapeutically useful by targeting both compartments at the same time.

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“…Namely, it was shown that exogenous or endogenous cannabinoid and vanilloid ligands induced in vitro growthinhibition and (apoptotic or necrotic) cell death of the PCC cell lines expressing CB1 and TRPV1 (Nithipatikom et al 2004;Sarfaraz et al 2005;Sanchez et al 2005Sanchez et al , 2006Mori et al 2006). Furthermore, recent reports presented that vanilloids in vivo eVectively prevented the growth or induced the regression of xenograft tumors induced by PCC-derived cell lines (Sanchez et al 2006;Mori et al 2006), similar to the action of cannabinoids on skin tumors (Casanova et al 2003).…”

Section: Introductionmentioning

confidence: 80%

Increased expressions of cannabinoid receptor-1 and transient receptor potential vanilloid-1 in human prostate carcinoma

Czifra

Varga

Nyeste

et al. 2008

J Cancer Res Clin Oncol

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Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors

Cited by 208 publications

References 34 publications

The non-psychoactive cannabidiol triggers caspase activation and oxidative stress in human glioma cells

The non-psychoactive cannabidiol triggers caspase activation and oxidative stress in human glioma cells

Critical role of extracellular vesicles in modulating the cellular effects of cytokines

Increased expressions of cannabinoid receptor-1 and transient receptor potential vanilloid-1 in human prostate carcinoma

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