The Interplay between the Immune and the Endocannabinoid Systems in Cancer

Braile, Mariantonia; Marcella, Simone; Marone, Gianni; Galdiero, Maria Rosaria; Varricchi, Gilda; Loffredo, Stefania

doi:10.3390/cells10061282

Cited by 33 publications

(13 citation statements)

References 304 publications

(434 reference statements)

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Section: Figurementioning

confidence: 99%

“…The stimulation of CBRs regulates different biological actions on cells of the adaptive and innate immune system. The expression of CB2Rs and CB1Rs on different subsets of immune cells in TME could be relevant in tumor progression [120] (Figure 2). Regarding the antineoplastic mechanism of action of other new CBs, a study published on the cannabinoid properties of a new family of chromenopyrazoles showed that fully selective CB1R ligand lacked psychoactive effects.…”

Section: Figurementioning

confidence: 99%

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Pros and Cons of the Cannabinoid System in Cancer: Focus on Hematological Malignancies

et al. 2021

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The endocannabinoid system (ECS) is a composite cell-signaling system that allows endogenous cannabinoid ligands to control cell functions through the interaction with cannabinoid receptors. Modifications of the ECS might contribute to the pathogenesis of different diseases, including cancers. However, the use of these compounds as antitumor agents remains debatable. Pre-clinical experimental studies have shown that cannabinoids (CBs) might be effective for the treatment of hematological malignancies, such as leukemia and lymphoma. Specifically, CBs may activate programmed cell death mechanisms, thus blocking cancer cell growth, and may modulate both autophagy and angiogenesis. Therefore, CBs may have significant anti-tumor effects in hematologic diseases and may synergistically act with chemotherapeutic agents, possibly also reducing chemoresistance. Moreover, targeting ECS might be considered as a novel approach for the management of graft versus host disease, thus reducing some symptoms such as anorexia, cachexia, fatigue, anxiety, depression, and neuropathic pain. The aim of the present review is to collect the state of the art of CBs effects on hematological tumors, thus focusing on the essential topics that might be useful before moving into the clinical practice.

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Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Pros and Cons of the Cannabinoid System in Cancer: Focus on Hematological Malignancies

et al. 2021

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“…Compared with healthy tissues, the expression of cannabinoid receptors is altered in tumours [102], and the effects of cannabinoids therefore vary among cancer cell lines. A detailed review of the mechanisms is beyond the scope of this article; the complexity of the ECS in cancer has recently been reviewed elsewhere [103].…”

Section: Mechanismmentioning

confidence: 99%

Cannabidiol and Other Phytocannabinoids as Cancer Therapeutics

Nahler

2022

Pharm Med

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Preclinical models provided ample evidence that cannabinoids are cytotoxic against cancer cells. Among the best studied phytocannabinoids, cannabidiol (CBD) is most promising for the treatment of cancer as it lacks the psychotomimetic properties of delta-9-tetrahydrocannabinol (THC). In vitro studies and animal experiments point to a concentration-(dose-) dependent anticancer effect. The effectiveness of pure compounds versus extracts is the subject of an ongoing debate. Actual results demonstrate that CBD-rich hemp extracts must be distinguished from THC-rich cannabis preparations. Whereas pure CBD was superior to CBD-rich extracts in most in vitro experiments, the opposite was observed for pure THC and THC-rich extracts, although exceptions were noted. The cytotoxic effects of CBD, THC and extracts seem to depend not only on the nature of cannabinoids and the presence of other phytochemicals but also largely on the nature of cell lines and test conditions. Neither CBD nor THC are universally efficacious in reducing cancer cell viability. The combination of pure cannabinoids may have advantages over single agents, although the optimal ratio seems to depend on the nature of cancer cells; the existence of a 'one size fits all' ratio is very unlikely. As cannabinoids interfere with the endocannabinoid system (ECS), a better understanding of the circadian rhythmicity of the ECS, particularly endocannabinoids and receptors, as well as of the rhythmicity of biological processes related to the growth of cancer cells, could enhance the efficacy of a therapy with cannabinoids by optimization of the timing of the administration, as has already been reported for some of the canonical chemotherapeutics. Theoretically, a CBD dose administered at noon could increase the peak of anandamide and therefore the effects triggered by this agent. Despite the abundance of preclinical articles published over the last 2 decades, well-designed controlled clinical trials on CBD in cancer are still missing. The number of observations in cancer patients, paired with the anticancer activity repeatedly reported in preclinical in vitro and in vivo studies warrants serious scientific exploration moving forward.

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“…These receptors are expressed on several immune cell populations, and conceivably, they modulate a variety of functions of innate and adaptive immune systems. The full characterization of the human cannabinoid receptor pathways has been only recently completed and is opening the way to future anticancer therapeutic approaches targeting this receptor, based on the specific design of CB1 and CB2 agonists [26].…”

Section: Other Therapeutic Approaches For Cancer Abolitionmentioning

confidence: 99%