Regulation of inflammation and proliferation of human bladder carcinoma cells by type-1 and type-2 cannabinoid receptors

Gasperi, Valeria; Evangelista, D; Oddi, Sergio; Florenzano, Fulvio; Chiurchiù, Valerio; Avigliano, Luciana; Catani, Maria Valeria; Maccarrone, Mauro

doi:10.1016/j.lfs.2014.09.031

Cited by 19 publications

(14 citation statements)

References 61 publications

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“…The alteration in the ECS activity during tumor onset and progression and its involvement in bladder cancer has been demonstrated in cellular models [17][18][19]. On the other hand, to date no data are available on the quantification of ECs and NAEs levels in the urine of healthy subjects or patients with bladder cancer.…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown successfully that ECs can act by several different cellular mechanisms, including inhibition of cell proliferation, migration and progression; inhibition of angiogenesis; and promotion of apoptosis and/or cell cycle arrest [13][14][15][16]. In addition, the EC involvement in bladder cancer proliferation and progression has been demonstrated in ECV304 [17], RT4, RT112 [18], 5637, and HT-1376 [19] cellular models resembling different tumor grades. Starting from this knowledge, a possible modification in ECs and NAEs levels in urine from patients with bladder cancer can be hypothesized.…”

Section: Introductionmentioning

confidence: 99%

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Urine Endocannabinoids as Novel Non-Invasive Biomarkers for Bladder Cancer at Early Stage

Vago

Ravelli

Bettiga

et al. 2020

Cancers

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Due to the involvement of the endocannabinoid system (ECS) in cancer onset and progression and the less studied connection between ECS and bladder cancer, here an evaluation of the ECS modifications associated with bladder cancer is reported. Urine samples were collected from healthy volunteers and patients with bladder cancer at different grades. Endocannabinoids (ECs) and N-acylethanolamides (NAEs) were quantified by HPLC-MS/MS and results normalized for creatinine content. An increase in the urine concentrations of four ECs and NAEs analyzed was observed with a statistically significant increase in the arachidonoylethanolamide (AEA) and stearoylethanoamide (SEA) associated with bladder cancer. Receiver operating characteristic curves built with AEA and SEA data allowed the selection of 160 pg/mL for SEA (area under the curve (AUC) = 0.91, Selectivity (SE) 94%, Specificity (SP) 45%) and 8 pg/mL for AEA (AUC = 0.85, SE 94%, SP 61%) as the best cut-off values. Moreover, data from bladder cancer samples at different grades were derived from The Cancer Genome Atlas, and the expressions of thirteen different components of the “endocannabinoidome” were analyzed. Statistical analysis highlights significant variations in the expression of three enzymes involved in EC and NAE turnover in bladder cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Urine Endocannabinoids as Novel Non-Invasive Biomarkers for Bladder Cancer at Early Stage

Vago

Ravelli

Bettiga

et al. 2020

Cancers

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“…Here CB 2 R and TSPO were used as examples. Both CB 2 R and TSPO are overexpressed in many cancers, such as breast [41, 54] [55, 56], bladder [57] prostate [43, 58], colorectal [42, 43] cancer. In addition, the higher expression level of CB 2 R and TSPO correlate with tumor aggressive and poorer prognosis, and both are considered to be the target of cancer therapy [59–61].…”

Section: Discussionmentioning

confidence: 99%

Multilayer photodynamic therapy for highly effective and safe cancer treatment

et al. 2017

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Recent efforts to develop tumor-targeted photodynamic therapy (PDT) photosensitizers (PSs) have greatly advanced the potential of PDT in cancer therapy, although complete eradication of tumor cells by PDT alone remains challenging. As a way to improve PDT efficacy, we report a new combinatory PDT therapy technique that specifically targets multilayers of cells. Simply mixing different PDT PSs, even those that target distinct receptors (this may still lead to similar cell-killing pathways), may not achieve ideal therapeutic outcomes. Instead, significantly improved outcomes likely require synergistic therapies that target various cellular pathways. In this study, we target two proteins upregulated in cancers: the cannabinoid CB2 receptor (CB2R, a G-protein coupled receptor) and translocator protein (TSPO, a mitochondria membrane receptor). We found that the CB2R-targeted PS, IR700DX-mbc94, triggered necrotic cell death upon light irradiation, whereas PDT with the TSPO-targeted IR700DX-6T agent led to apoptotic cell death. Both PSs significantly inhibited tumor growth in vivo in a target-specific manner. As expected, the combined CB2R- and TSPO-PDT resulted in enhanced cell killing efficacy and tumor inhibition with lower drug dose. The median survival time of animals with multilayer PDT treatment was extended by as much as 2.8-fold over single PDT treatment. Overall, multilayer PDT provides new opportunities to treat cancers with high efficacy and low side effects.

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“…18 There is an abundance of current literature pointing to the role of chronic inflammatory states in the development and progression of cancer, as well as the ability of tumour cells to metastasize. Furthermore, previous literature has shown that cancer cells can trigger release of inflammatory cells, such as cytokines and growth factors, that create a pro-inflammatory microenvironment often correlated to the highly invasive phenotype and metastatic potential of cancer.…”

Section: Cannabinoids and Bladder Cancermentioning

confidence: 99%

“…The study demonstrated bladder cancer cell lines were regulated by activation of CB receptors where CB1 receptor activation played a more prominent role in proliferation and CB2 receptors were more effective in triggering the pro-inflammatory state. 18 Further research and more studies are required to understand the expression of these receptors in different stages of bladder cancers and also the varying effect of endocannabinoid ligands on the different CB1 and CB2 receptors.…”

Section: Cannabinoids and Bladder Cancermentioning

confidence: 99%

Systematic review of the potential role of cannabinoids as antiproliferative agents for urological cancers

Gandhi

Vasisth

Kapoor

2017

CUAJ

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Introduction: The palliative effects of cannabis sativa (marijuana), which include appetite stimulation, attenuation of nausea and emesis, and pain relief, are well known. The active components of cannabis sativa (cannabinoids) and their derivatives have received growing interest due to their diverse pharmacological activities, such as cell growth inhibition and tumour regression. The aim of this review is to look at the current evidence on the antiproliferative effects of cannabinoids in urological malignancies, including renal, prostate, bladder, and testicular cancers. Methods: We conducted a systematic review of studies exploring the effect of cannabinoids on tumour activity, including all study types except expert opinions. A formal search was run on Medline database from 1946 to September 2016, along with a hand-search on PubMed for relevant studies. Results: The search yielded a total of 93 studies from Medline and PubMed, of which 23 studies were included in the final analysis. To date, there are various in vitro studies elucidating the potential mechanism of action of cannabinoids for urological cancers, along with population-based studies specifically for testicular malignancies. To date, no clinical trials have been conducted for urological cancer patients.Conclusions: These results demonstrate that the role of endocannabinoids for urological malignancies is an area of active research. Further research is required not only to evaluate the crosstalk between cancer signaling pathways and cannabinoids, but also large randomized clinical studies with urological patients need to be conducted before cannabinoids can be introduced as potential therapeutic options for urological neoplasms.

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Regulation of inflammation and proliferation of human bladder carcinoma cells by type-1 and type-2 cannabinoid receptors

Cited by 19 publications

References 61 publications

Urine Endocannabinoids as Novel Non-Invasive Biomarkers for Bladder Cancer at Early Stage

Urine Endocannabinoids as Novel Non-Invasive Biomarkers for Bladder Cancer at Early Stage

Multilayer photodynamic therapy for highly effective and safe cancer treatment

Systematic review of the potential role of cannabinoids as antiproliferative agents for urological cancers

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