Abstract To assess the effect of Cannabidiol (CBD) on the angiogenesis and stemness of breast cancer cells as well as proliferation. Methods: mRNA level and the amount of protein of vascular endothelial growth factor (VEGF) were determined by qRT-PCR and ELISA. The angiogenic potential of breast cancer cells under hypoxic conditions was identified by the HUVEC tube formation assay. The degradation of HIF-1α by CBD and the Src/von Hippel–Lindau tumor suppressor protein (VHL) interaction were assessed by a co-immunoprecipitation assay and Western blotting. To identify the stemness of mamospheres, they were evaluated by the sphere-forming assay and flow cytometry. Results: CBD can suppress angiogenesis...

Please use this link to access this publication. Abstract Background: We previously reported that cannabidiol (CBD), a cannabinoid with a low toxicity profile, downregulated the expression of the prometastatic gene inhibitor of DNA binding 1 (ID1) in cancer cells, leading to inhibition of tumor progression in vivo. While CBD is broadly used, including in the self-medication of cancer patients, and CBD-based therapies are undergoing clinical evaluation for cancer treatment, its mechanisms of action are still poorly understood. Methods: In this study, using microarray analysis and Western blot analysis for validation, we attempted to identify the full spectrum of genes regulated by CBD across various...

Abstract Cannabidiol (CBD), a phytochemical derived from Cannabis sativa L., has been demonstrated to exhibit promising anti-tumor properties in multiple cancer types. However, the effects of CBD on hepatocellular carcinoma (HCC) cells remain unknown. We have shown that CBD effectively suppresses HCC cell growth in vivo and in vitro, and induced HCC cell pyroptosis in a caspase-3/GSDME-dependent manner. We further demonstrated that accumulation of integrative stress response (ISR) and mitochondrial stress may contribute to the initiation of pyroptotic signaling by CBD. Simultaneously, CBD can repress aerobic glycolysis through modulation of the ATF4–IGFBP1–Akt axis, due to the depletion of ATP and crucial intermediate metabolites. Collectively,...

ABSTRACT Glioma is the most common primary malignant brain tumor with poor survival and limited therapeutic options. The non-psychoactive phytocannabinoid cannabidiol (CBD) has been shown to be effective against glioma; however, the molecular target and mechanism of action of CBD in glioma are poorly understood. Here we investigated the molecular mechanisms underlying the antitumor effect of CBD in preclinical models of human glioma. Our results showed that CBD induced autophagic rather than apoptotic cell death in glioma cells. We also showed that CBD induced mitochondrial dysfunction and lethal mitophagy arrest, leading to autophagic cell death. Mechanistically, calcium flux induced by CBD through TRPV4 (transient...

Abstract As the major nonpsychotropic constituent of Cannabis sativa, cannabidiol (CBD) is regarded as one of the most promising therapeutic agents due to its proven effectiveness in clinical trials for many human diseases. Due to the urgent need for more efficient pharmacological treatments for several chronic diseases, in this review, we discuss the potential beneficial effects of CBD for Alzheimer’s disease, epilepsy, multiple sclerosis, and neurological cancers. Due to its wide range of pharmacological activities (e.g., antioxidant, anti-inflammatory, and neuroprotective properties), CBD is considered a multimodal drug for the treatment of a range of neurodegenerative disorders, and various cancer types, including neoplasms of the...

Please use this link to access this publication. Abstract Low tetrahydrocannabinol Cannabis sativa products, also known as hemp products, have become widely available and their use in veterinary patients has become increasingly popular. Despite prevalence of use, the veterinary literature is lacking and evidence-based resource for cannabinoid efficacy. The most prevailing cannabinoid found in hemp is cannabidiolic acid (CBDA) and becomes cannabidiol (CBD) during heat extraction; CBD has been studied for its direct anti-neoplastic properties alone and in combination with standard cancer therapies, yielding encouraging results. The objectives of our study were to explore the anti-proliferative and cell death response associated with in vitro...

Please use this link to access this publication. Abstract Cannabidiol (CBD) has been shown to slow cancer cell growth and is toxic to human glioblastoma cell lines. Thus, CBD could be an effective therapeutic for glioblastoma. In the present study, we explored the anticancer effect of cannabidiol loaded magnesium-gallate (CBD/Mg-GA) metal–organic framework (MOF) using the rat glioma brain cancer (C6) cell line. Bioactive and microporous magnesium gallate MOF was employed for simultaneous delivery of two potential anticancer agents (gallic acid and CBD) to the cancer cells. Gallic acid (GA), a polyphenolic compound, is part of the MOF framework, while CBD is loaded within the...

Please use this link to access this publication. Abstract Extracellular Vesicles (EVs) were isolated from human umbilical cord mesenchymal stem cells (hUCMSCs) and were further encapsulated with cannabidiol (CBD) through sonication method (CBD EVs). CBD EVs displayed an average particle size of 114.1 ± 1.02 nm, zeta potential of −30.26 ± 0.12 mV, entrapment efficiency of 92.3 ± 2.21% and stability for several months at 4 °C. CBD release from the EVs was observed as 50.74 ± 2.44% and 53.99 ± 1.4% at pH 6.8 and pH 7.4, respectively after 48 h. Our in-vitro studies demonstrated that CBD either alone or in EVs form...

Abstract Chemotherapy-induced peripheral neurotoxicity (CIPN) is one of the most frequent side effects of antineoplastic treatment, particularly of lung, breast, prostate, gastrointestinal, and germinal cancers, as well as of different forms of leukemia, lymphoma, and multiple myeloma. Currently, no effective therapies are available for CIPN prevention, and symptomatic treatment is frequently ineffective; thus, several clinical trials are addressing this unmet clinical need. Among possible pharmacological treatments of CIPN, modulation of the endocannabinoid system might be particularly promising, especially in those CIPN types where analgesia and neuroinflammation modulation might be beneficial. In fact, several clinical trials are ongoing with the specific aim to better investigate...

Abstract Cancer, as a mysterious and complex disease, has a multi-stage molecular process that uses the cellular molecular machine and multiple signaling pathways to its advantage. Cannabinoids, as terpenophenolic compounds and their derivatives, showed influences on immune system responses, inflammation, and cell growth that have sparked a growing interest in exploring their effects on cancer cell fate, as well. A large body of evidence in experimental models indicating the involvement of cannabinoids and their related receptors in cancer cell growth, development, and fate. In accordance, the present study provided insights regarding the strengths and limits of cannabinoids and their receptors in critical steps of...