Plant-derived cannabinoids as anticancer agents

O’Reilly, Eve; Cosgrave, Joanne M.; Perry, Antoinette S.

doi:10.1016/j.trecan.2022.01.017

Cited by 10 publications

(4 citation statements)

References 15 publications

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“…The molecular mechanisms of cannabinoid action in glioblastoma are complex and involve both receptor-dependent and -independent pathways. In addition to the modulation of the ECS and downstream signalling pathways, cannabinoids can also interact with other targets, such as ion channels, other G proteincoupled receptors, and nuclear receptors [130][131][132][133]. An increasing number of preclinical models and clinical studies have investigated the anti-cancer effects of cannabinoids on a variety of cancers [134].…”

Section: Eicosanoidsmentioning

confidence: 99%

Targeting the Endocannabinoid System Present in the Glioblastoma Tumour Microenvironment as a Potential Anti-Cancer Strategy

Dasram,

Naidoo,

Walker

et al. 2024

IJMS

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The highly aggressive and invasive glioblastoma (GBM) tumour is the most malignant lesion among adult-type diffuse gliomas, representing the most common primary brain tumour in the neuro-oncology practice of adults. With a poor overall prognosis and strong resistance to treatment, this nervous system tumour requires new innovative treatment. GBM is a polymorphic tumour consisting of an array of stromal cells and various malignant cells contributing to tumour initiation, progression, and treatment response. Cannabinoids possess anti-cancer potencies against glioma cell lines and in animal models. To improve existing treatment, cannabinoids as functionalised ligands on nanocarriers were investigated as potential anti-cancer agents. The GBM tumour microenvironment is a multifaceted system consisting of resident or recruited immune cells, extracellular matrix components, tissue-resident cells, and soluble factors. The immune microenvironment accounts for a substantial volume of GBM tumours. The barriers to the treatment of glioblastoma with cannabinoids, such as crossing the blood–brain barrier and psychoactive and off-target side effects, can be alleviated with the use of nanocarrier drug delivery systems and functionalised ligands for improved specificity and targeting of pharmacological receptors and anti-cancer signalling pathways. This review has shown the presence of endocannabinoid receptors in the tumour microenvironment, which can be used as a potential unique target for specific drug delivery. Existing cannabinoid agents, studied previously, show anti-cancer potencies via signalling pathways associated with the hallmarks of cancer. The results of the review can be used to provide guidance in the design of future drug therapy for glioblastoma tumours.

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Section: Eicosanoidsmentioning

confidence: 99%

Targeting the Endocannabinoid System Present in the Glioblastoma Tumour Microenvironment as a Potential Anti-Cancer Strategy

Dasram,

Naidoo,

Walker

et al. 2024

IJMS

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“…An interest in the potential use of derivates of plant species belonging to the Cannabis genus has increased considerably in recent decades [1,2]. Various in vitro experiments, in vivo preclinical investigations, and clinical studies indicate that some secondary metabolites of these plants reveal promising activity for use not only in the palliative care of cancer patients as pain-relievers [3][4][5] but also in directly targeting the malignant cells and decreasing their viability [6][7][8][9]. Particular interest is paid to cannabinoids, lipophilic terpenophenolic molecules acting as ligands of a specific group of membrane G-proteincoupled receptors, known as cannabinoid receptors (CB receptors; CB1 and CB2), which, together with their endogenous ligands, constitute the endocannabinoid system (ES) [10].…”

Section: Introductionmentioning

confidence: 99%

In Vitro Evidence of Selective Pro-Apoptotic Action of the Pure Cannabidiol and Cannabidiol-Rich Extract

Śledziński,

Nowak-Terpiłowska,

Rzymski

et al. 2023

Molecules

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Plant cannabinoids, secondary metabolites of species belonging to the Cannabis genus, can mimic the endocannabinoids’ action and exert biological effects. Considering the contribution of the endocannabinoid system in cell cycle and apoptotic regulation, there is an interest in exploring the potential anti-cancer activities of natural and synthetic cannabinoids. Cannabidiol (CBD), an abundant plant cannabinoid, reveals a low affinity to cannabinoid receptors and, contrary to various cannabinoids, lacks psychoactive action. Here, we present the in vitro assessment of the pro-apoptototic potential of CBD-rich extracts of Cannabis sativa L. (eCBD) compared to purified CBD (pCBD). As demonstrated, both eCBD and pCBD decreased the viability of breast cancer cell line MDA-MB-231 and human prostate cancer cell line PC-3 in a concentration-dependent fashion. Endoplasmic reticulum stress-related apoptosis and morphological changes were induced only in low-serum conditions. Moreover, the effects of eCDB and pCDB were also assessed in non-malignant cell lines (MCF-10A and PNT2) with no alterations of viability noted, ultimately suggesting a selective action of CBD in tumor cells. The results suggest the possible involvement of reactive oxygen species in the response mechanism to eCBD and pCBD, but no clear pattern was observed. We also demonstrated significant changes in gene expression involved in apoptosis and cell cycle control upon extract treatment. Altogether, our study shows the potential of eCBD and pCBD as novel pro-apoptototic agents that can be considered promising in future preclinical and clinical testing.

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“…However, accumulating evidence demonstrated phytocannabinoids directly affect tumor development in cell lines and animal models by modulating key cell-signaling pathways (18)(19)(20). Studies demonstrated that purified phytocannabinoids can inhibit proliferation, metastasis, and angiogenesis and exert pro-apoptotic effects in a variety of cancer cell types such as lung, breast, prostate, skin, intestine, glioma, lymphoma, pancreas and uterine cancers (21)(22)(23). In preclinical models, treatment with phytocannabinoids led to tumor regression of different cancer types (24,25).…”

Section: Introductionmentioning

confidence: 99%

Cannabinoid Combination TargetsNOTCH1-Mutated T-ALL Through the Integrated Stress Response Pathway

Besser,

Gelfand,

Procaccia

et al. 2023

Preprint

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In T-cell acute lymphoblastic leukemia (T-ALL) more than 50% of cases display autoactivation of Notch1 signaling, leading to oncogenic transformation. We have previously identified a specific chemovar of Cannabis that induces apoptosis by preventing Notch1 maturation in leukemia cells. Here, we isolated three cannabinoids from this chemovar that synergistically mimic the effects of the whole extract. Two were previously known, Cannabidiol (CBD) and Cannabidivarin (CBDV); whereas the third cannabinoid, which we termed 331-18A, was identified and fully characterized in this study. We demonstrated that these cannabinoids act through Cannabinoid receptor type 2 and TRPV1 to activate the integrated stress response pathway by depleting intracellular Ca2+. This is followed by increased mRNA and protein expression of ATF4, CHOP and CHAC1, which is hindered by inhibiting the upstream initiation factor eIF2α. The increased abundance of CHAC1 prevents Notch1 maturation, thereby reducing the levels of the active Notch1 intracellular domain, and consequently decreasing cell viability and increasing apoptosis. Treatment with the three isolated molecules resulted in reduced tumor size and weight in-vivo and slowed leukemia progression in mice models. Altogether, this study elucidated the mechanism of action of three distinct cannabinoids in modulating the Notch1 pathway, and constitutes an important step in the establishment of a new therapy for treatingNOTCH1-mutated diseases and cancers such as T-ALL.

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Plant-derived cannabinoids as anticancer agents

Cited by 10 publications

References 15 publications

Targeting the Endocannabinoid System Present in the Glioblastoma Tumour Microenvironment as a Potential Anti-Cancer Strategy

Targeting the Endocannabinoid System Present in the Glioblastoma Tumour Microenvironment as a Potential Anti-Cancer Strategy

In Vitro Evidence of Selective Pro-Apoptotic Action of the Pure Cannabidiol and Cannabidiol-Rich Extract

Cannabinoid Combination TargetsNOTCH1-Mutated T-ALL Through the Integrated Stress Response Pathway

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