Emerging therapeutic targets in cancer induced bone disease: A focus on the peripheral type 2 cannabinoid receptor

Marino, Silvia; Idris, Aymen I.

doi:10.1016/j.phrs.2017.02.023

Cited by 33 publications

(24 citation statements)

References 180 publications

(229 reference statements)

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“…Patients with primary bone cancer, like OS, and bone metastases commonly acquire cancer-induced bone disease (CIBD), presenting several troubles such as bone pain, restricted mobility, high rate of fractures, nerve compression, and hypercalcemia. It has been observed that pharmacological and genetic manipulation of CB2 reduces the progression of CIBD [107]. In particular, its activation with specific ligands acts directly on tumor-inducing apoptosis or necrosis in malignant cells, but also on osteoclasts, inhibiting their formation and differentiation.…”

Section: Endocannabinoid/endovanilloid System In Bone Cancermentioning

confidence: 99%

The Endocannabinoid/Endovanilloid System in Bone: From Osteoporosis to Osteosarcoma

Rossi

Tortora

Punzo

et al. 2019

IJMS

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Bone is a dynamic tissue, whose homeostasis is maintained by a fine balance between osteoclast (OC) and osteoblast (OB) activity. The endocannabinoid/endovanilloid (EC/EV) system’s receptors are the cannabinoid receptor type 1 (CB1), the cannabinoid receptor type 2 (CB2), and the transient receptor potential cation channel subfamily V member 1 (TRPV1). Their stimulation modulates bone formation and bone resorption. Bone diseases are very common worldwide. Osteoporosis is the principal cause of bone loss and it can be caused by several factors such as postmenopausal estrogen decrease, glucocorticoid (GC) treatments, iron overload, and chemotherapies. Studies have demonstrated that CB1 and TRPV1 stimulation exerts osteoclastogenic effects, whereas CB2 stimulation has an anti-osteoclastogenic role. Moreover, the EC/EV system has been demonstrated to have a role in cancer, favoring apoptosis and inhibiting cell proliferation. In particular, in bone cancer, the modulation of the EC/EV system not only reduces cell growth and enhances apoptosis but it also reduces cell invasion and bone pain in mouse models. Therefore, EC/EV receptors may be a useful pharmacological target in the prevention and treatment of bone diseases. More studies to better investigate the biochemical mechanisms underlining the EC/EV system effects in bone are needed, but the synthesis of hybrid molecules, targeting these receptors and capable of oppositely regulating bone homeostasis, seems to be a promising and encouraging prospective in bone disease management.

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Section: Endocannabinoid/endovanilloid System In Bone Cancermentioning

confidence: 99%

The Endocannabinoid/Endovanilloid System in Bone: From Osteoporosis to Osteosarcoma

Rossi

Tortora

Punzo

et al. 2019

IJMS

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“…Another report has depicted that CBR deficiency could restrain loss of bone [32,36]. Growing data have disclosed that targetting CB 2 R in the bone possesses potential efficacy in the reduction in bone syndrome related to cancer [33]. In spite of this, there are no data available to date concerning the function of MDA19 on OS.…”

Section: Discussionmentioning

confidence: 99%

Anti-tumoral potential of MDA19 in human osteosarcoma via suppressing PI3K/Akt/mTOR signaling pathway

Liu

Dai

et al. 2018

Bioscience Reports

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Osteosarcoma (OS) is the most common primary malignancy of skeleton with higher mortality rates amongst children and young adults worldwide, whereas effective and secure therapies have also been sought by researches with ongoing efforts. The purpose of the present study was to investigate the impact of N′-[(3Z)-1-(1-hexyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene] benzohydrazide (MDA19) on OS and explore its potential mechanism. Cell Counting Kit-8 (CCK8) and colony formation assay were employed to evaluate the potential effect of MDA19 on U2OS and MG-63 cells proliferation. Moreover, transwell migration and invasion assay were performed to assess the influence of MDA19 on U2OS and MG-63 cells migration and invasion. In addition, Annexin V-FITC/propidium iodide (Annexin V-FITC/PI) staining and flow cytometry were used to examine apoptotic ratio of the U2OS and MG-63 cells. Meanwhile, Western blot analysis was applied to explore change of relevant mechanism proteins in OS cells treated with MDA19. Our study showed that MDA19 had anti-proliferative activity of OS cells in a dose- and time-dependent manner, simultaneously, inhibition of colony formation was also observed in U2OS and MG-63 cells after incubation of MDA19. Besides, MDA19 could significantly inhibit the number of migrated and invaded OS cells and markedly increase the OS cells apoptosis rate. Mechanistically, we detected detectable reductions in apoptosis related proteins, epithelial–mesenchymal transition (EMT)-related proteins and activity of phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling in U2OS and MG-63 cells exposure to MDA19. Overall, the current study indicates in vitro anti-proliferative, anti-metastatic, and pro-apoptotic potential of MDA19 in U2OS and MG-63 cells. Our findings propose a clue for further studies with this compound in preclinical and clinical treatment for OS.

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“…and AM630 have more specific actions on effector cells and tissues by targeting CB2 receptors (Marino & Idris, 2017).…”

Section: Synthetic Cannabinoidsmentioning

confidence: 99%

The effects of cannabis use on oral health

Liu

Yang

et al. 2019

Oral Diseases

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Cannabis, also known as marijuana, is one of the most commonly used substances for medical and recreational purposes globally. With the trend of global legalization of medical use of cannabis and even the recreational use, the prevalence of recreational use of cannabis has increased markedly over the past few years. Correspondingly, the potential health concerns related to cannabis consumption have also increased. Therefore, it is necessary for oral healthcare providers to understand the effects of cannabis use on oral health. This review briefly summarizes the components of cannabis, biologic activities on tissues, and mechanisms of action in human cells and tissues. Oral tissue expression of cannabinoid receptors and the potential association of cannabis to oral diseases are also examined. The goals of this review are to (1) elaborate the basic biology and physiology of cannabis in human oral tissues, and (2) provide a better understanding the effects of its use and abuse on oral health. Due to insufficient information, more well‐designed studies should be conducted. It is urgent to include cannabis usage into dental patient health records.

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Emerging therapeutic targets in cancer induced bone disease: A focus on the peripheral type 2 cannabinoid receptor

Cited by 33 publications

References 180 publications

The Endocannabinoid/Endovanilloid System in Bone: From Osteoporosis to Osteosarcoma

The Endocannabinoid/Endovanilloid System in Bone: From Osteoporosis to Osteosarcoma

Anti-tumoral potential of MDA19 in human osteosarcoma via suppressing PI3K/Akt/mTOR signaling pathway

The effects of cannabis use on oral health

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