Modulation of the tumor microenvironment and inhibition of EGF/EGFR pathway: Novel anti‐tumor mechanisms of Cannabidiol in breast cancer

Elbaz, Mohamad; Nasser, Mohd W.; Ravi, Janani; Wani, Nissar Ahmad; Ahirwar, Dinesh K.; Zhao, Helong; Oghumu, Steve; Satoskar, Abhay R.; Shilo, Konstantin; Carson, William E.; Ganju, Ramesh K.

doi:10.1016/j.molonc.2014.12.010

Cited by 176 publications

(159 citation statements)

References 58 publications

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“…Other recent studies indicated that CBD significantly inhibits epidermal growth factor (EGF)-induced proliferation and chemotaxis of breast cancer cells. In addition, it was shown that CBD inhibits EGF-induced activation of EGFR, ERK, AKT and NF-kB signaling pathways as well as MMP2 and MMP9 secretion (Elbaz et al, 2015). CBD also inhibited tumour growth and metastasis in different mouse model systems.…”

Section: Cannabinoids and Breast Cancermentioning

confidence: 98%

“…CBD also inhibited tumour growth and metastasis in different mouse model systems. Analysis of molecular mechanisms revealed that CBD significantly inhibits the recruitment of tumour-associated macrophages in primary tumour stroma and secondary lung metastases (Elbaz et al, 2015). Figure 3 summarizes the important pathways in cannabinoid induced cytotoxicity.…”

Section: Cannabinoids and Breast Cancermentioning

confidence: 99%

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Cannabinoid pharmacology in cancer research: A new hope for cancer patients?

Javid

Phillips

Afshinjavid

et al. 2016

European Journal of Pharmacology

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Cannabinoids have been used for many centuries to ease pain and in the past decade, the endocannabinoid system has been implicated in a number of pathophysiological conditions, such as mood and anxiety disorders, movement disorders such as Parkinson's and Huntington's disease, neuropathic pain, multiple sclerosis, spinal cord injury, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity, and osteoporosis. Several studies have demonstrated that cannabinoids also have anti-cancer activity and as cannabinoids are usually well tolerated and do not produce the typical toxic effects of conventional chemotherapies, there is considerable merit in the development of cannabinoids as potential anticancer therapies. Whilst the presence of psychoactive effects of cannabinoids could prevent any progress in this field, recent studies have shown the value of the non-psychoactive components of cannabinoids in activating apoptotic pathways, inducing anti-proliferative and anti-angiogenic effects. The aforementioned effects are suggested to be through pathways such as ERK, Akt, mitogen-activated protein kinase (MAPK) pathways, phosphoinositide 3-kinase (PI3K) pathways and hypoxia inducible factor 1 (HIF1), all of which are important contributors to the hallmarks of cancer. Many important questions still remain unanswered or are poorly addressed thus necessitating further research at basic pre-clinical and clinical levels. In this review, we address these issues with a view to identifying the key challenges that future research needs to address.

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Section: Cannabinoids and Breast Cancermentioning

confidence: 98%

Section: Cannabinoids and Breast Cancermentioning

confidence: 99%

Cannabinoid pharmacology in cancer research: A new hope for cancer patients?

Javid

Phillips

Afshinjavid

et al. 2016

European Journal of Pharmacology

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“…Furthermore, CBD is able to inhibit cancer cell invasion and metastasis (478,548,715). These actions, in highly aggressive human breast cancer cells, are in part mediated by inhibition of epidermal growth factor (EGF), NF-B, ERK/AKT, and matrix metalloproteinase 2 and 9 signaling pathways (238). CBD also reduces angiogenesis through actions on both tumor and endothelial cells (809) (FIGURE 1).…”

Section: Cancermentioning

confidence: 99%

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

Ligresti¹,

Petrocellis²,

Marzo³

2016

Physiological Reviews

337

312

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Apart from having been used and misused for at least four millennia for, among others, recreational and medicinal purposes, the cannabis plant and its most peculiar chemical components, the plant cannabinoids (phytocannabinoids), have the merit to have led humanity to discover one of the most intriguing and pleiotropic endogenous signaling systems, the endocannabinoid system (ECS). This review article aims to describe and critically discuss, in the most comprehensive possible manner, the multifaceted aspects of 1) the pharmacology and potential impact on mammalian physiology of all major phytocannabinoids, and not only of the most famous one ⌬ 9 -tetrahydrocannabinol, and 2) the adaptive prohomeostatic physiological, or maladaptive pathological, roles of the ECS in mammalian cells, tissues, and organs. In doing so, we have respected the chronological order of the milestones of the millennial route from medicinal/recreational cannabis to the ECS and beyond, as it is now clear that some of the early steps in this long path, which were originally neglected, are becoming important again. The emerging picture is rather complex, but still supports the belief that more important discoveries on human physiology, and new therapies, might come in the future from new knowledge in this field.

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“…Our studies showed that LDHA downregulation inhibits cell migration, invasion and tube formation. Furthermore, our data showed that depletion of LDHA decreased the expression of MMP-2 and MMP-9, suggesting that LDHA may be involved in RCC invasion through inducing enzyme-based degradation of the extracellular matrix [23,24] . Furthermore, it is worth noting that LDHA depletion with siRNA leads to diminished VEGF and VE-cadherin levels, which are known to modulate vascular angiogenesis [25] and tumor development [26,27] .…”

Section: Discussionmentioning

confidence: 64%

Inhibition of LDHA Deliver Potential Anticancer Performance in Renal Cell Carcinoma

Wang

et al. 2016

Urol Int

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Purpose: Lactate dehydrogenase A (LDHA), which functions as a crucial enzyme in transforming from pyruvate into lactate, has been reported to be overexpressed in various advanced cancer and its silencing has turned out to be tumor suppressive. Previous studies have showed that the expression of LDHA was higher in renal cell carcinoma (RCC) than that in corresponding normal renal tissue. However, the function of LDHA in RCC, and its possible mechanism in tumor progression, has not been investigated. Methods: MTT and cell cycle assay were performed to explore the growth of the renal cells. Transwell assay for the migration and invasion and tube formation were conducted to detect the metastatic properties of the renal cancer. Results: Here, we show that siRNA-mediated knockdown of LDHA inhibits cell proliferation by decreasing cell cycle and promoting apoptosis in renal cancer cell lines. Mechanistically, LDHA siRNA treatment altered the expression of cell cycle- and apoptosis-related proteins, including p21, cyclin D1, Bcl-2 and Bax. In addition, LDHA siRNA treatment leads to markedly diminished migratory and invasive ability by reducing the expression of matrix metalloproteinase (MMP)-2 and MMP-9. Conclusions: These findings are consistent with the view that LDHA, as an oncogene, might be a potential therapeutic target in RCC.

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Modulation of the tumor microenvironment and inhibition of EGF/EGFR pathway: Novel anti‐tumor mechanisms of Cannabidiol in breast cancer

Cited by 176 publications

References 58 publications

Cannabinoid pharmacology in cancer research: A new hope for cancer patients?

Cannabinoid pharmacology in cancer research: A new hope for cancer patients?

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

Inhibition of LDHA Deliver Potential Anticancer Performance in Renal Cell Carcinoma

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