Abstract Cholangiocarcinoma (CCA) is a rare and highly lethal disease with few effective treatment options. Cannabinoids, cannabidiol (CBD) and cannabigerol (CBG) are non-psychedelic components extracted from cannabis. These non-psychoactive compounds have shown anti-proliferative potential in other tumor models; however, the efficacy of CBD and CBG in CCA is unknown. Furthermore, two cell death pathways are implicated with CBD resulting in autophagic degeneration and CBG in apoptosis. HuCC-T1 cells, Mz-ChA-1 cells (CCA cell lines) and H69 cells (immortalized cholangiocytes), were treated with CBD and CBG for 24 to 48 h. The influence of these cannabinoids on proliferation was assessed via MTT assay. Apoptosis and cell...

Abstract There is currently a growing interest in the use of cannabidiol (CBD) to alleviate the symptoms caused by cancer, including pain, sleep disruption, and anxiety. CBD is often self-administered as an over-the-counter supplement, and patients have reported benefits from its use. However, despite the progress made, the mechanisms underlying CBD’s anti-cancer activity remain divergent and unclear. Herein, we provide a comprehensive review of molecular mechanisms to determine convergent anti-cancer actions of CBD from pre-clinical and clinical studies. In vitro studies have begun to elucidate the molecular targets of CBD and provide evidence of CBD’s anti-tumor properties in cell and mouse models of cancer....

Simple Summary Mesothelioma is a deadly disease with few treatment options. Phytocannabinoids derived from the cannabis plant are garnering interest for their anti-cancer properties, however very little is known about their effects in mesothelioma. We aimed to assess whether phytocannabinoids have anti-cancer effects in mesothelioma and potential modes of action. We showed that several phytocannabinoids inhibited growth of mesothelioma cells, with two phytocannabinoids, cannabidiol (CBD) and cannabigerol (CBG), being the most potent. CBD and CBG also inhibited mesothelioma cell migration and invasion. Gene expression analysis highlighted signalling pathways that play a role in how CBD and CBG may exert their anti-cancer effects. CBD and...

Please use this link to access this publication. Abstract To date, promising therapy for triple negative breast cancer (TNBC) remains a serious concern clinically because of poor prognosis, resistance, and recurrence. Herein, anti-cancer potential of synthetic cannabidiol (CBD; Purisys, GA; GMP grade) was explored either alone or as a chemosensitizer followed by post-treatment with doxorubicin (DOX) in TNBC (i.e., MDA-MB-231 and MDA-MB-468) cells. In comparison to 2D cultures, CBD showed greater IC50 values in 3D (LDP2 hydrogel based) cultures of MDA-MB-231 (6.26-fold higher) and MDA-MB-468 (10.22-fold higher) cells. Next-generation RNA sequencing revealed GADD45A, GADD45G, FASN, LOX, and integrin (i.e., -α5, -β5) genes to be novelly altered by CBD in...

Abstract One of the most common complications of cancer chemotherapy is oral mucositis (OM), a serious kind of oral ulceration, but its effective treatment remains a serious challenge. In this study, we used deoxycholic acid and fucoidan to prepare inflammation-targeting nanomicelles (FD), because fucoidan can target inflammation due to its high binding affinity for P-selectin. The hydrophobic anti-inflammatory drug cannabidiol (CBD) was then loaded into the hydrophobic core of FD. The resulting CBD-loaded FD micelles (CBD/FD) had uniform particle size and morphology, as well as favorable serum stability. Moreover, administration of the FD micelles via intravenous injection or in situ dripping in an OM mouse model enhanced the...

Abstract Phytocannabinoids possess anticancer properties, as established in vitro and in vivo. However, they are characterized by high lipophilicity. To improve the properties of cannabidiol (CBD), such as solubility, stability, and bioavailability, CBD inclusion complexes with cyclodextrins (CDs) might be employed, offering targeted, faster, and prolonged CBD release. The aim of the present study is to investigate the in vitro effects of CBD and its inclusion complexes in randomly methylated β-CD (RM-β-CD) and 2-hyroxypropyl-β-CD (HP-β-CD). The enhanced solubility of CBD upon complexation with CDs was examined by phase solubility study, and the structure of the inclusion complexes of CBD in 2,6-di-O-methyl-β-CD (DM-β-CD) and 2,3,6-tri-O-methyl-β-CD (TM-β-CD)...

Abstract Oral mucositis (OM) is a common complication during chemotherapy characterized by ulceration, mucosa atrophy, and necrosis, which seriously interferes with nutritional intake and oncotherapy procedures among patients. However, the efficacy of current treatments for OM remains limited. Cannabidiol (CBD) is a natural cannabinoid with multiple biological activities, including antioxidant and anti-inflammatory potential. In this study, we aimed to investigate the chemopreventive effects and mechanisms of CBD in protecting C57BL/6N mice and human oral keratinocytes (HOK) from 5-fluorouracil- (5-FU-) induced OM. Here, we found that CBD alleviated the severity of 5-FU-induced OM in mice, including improved survival, decreased body weight loss, reduced ulcer sizes,...

Simple Summary Drug resistance is the key factor contributing to the therapeutic failure of lung cancer and the deaths related to lung cancer. Our study demonstrated that small molecular weight non-psychotropic phytochemical, cannabidiol (CBD), inhibits growth and metastasis of drug-resistant non-small cell lung cancer cells (NSCLC) cells in-vitro and in-vivo. We further discovered that CBD mediates its anti-cancer effects in part via an ion channel receptor, TRPV2, present on lung adenocarcinoma. Moreover, we showed that CBD induces apoptosis of cisplatin-resistant cells by modulating oxidative stress pathways. Overall, these studies indicate that CBD could be used as a promising therapeutic strategy in TRPV2 expressing cisplatin-resistant...

Abstract Extracts of phytocannabinoids from Cannabis sativa have been studied for therapeutic purposes. Although nonpsychoactive CBD has been studied as a promising anticancer drug because it induces apoptosis in many cancer cells, it is also known to induce several physiological changes. In this study, we clarify the functional role it plays in the morphological characteristics of intracellular vesicle formation as well as apoptosis in A549 human lung cancer cells. CBD treatment shows growth inhibition at concentrations above 20 μM, but FACS analysis shows low efficacy in terms of cell death. Microscopic observations suggest that multiple vesicles were detected in the cytoplasmic region of CBD-treated A549 cells....

Abstract The medical application of cannabidiol (CBD) has been gathering increasing attention in recent years. This non-psychotropic cannabis-derived compound possesses antiepileptic, antipsychotic, anti-inflammatory and anxiolytic properties. Recent studies report that it also exerts antineoplastic effects in multiple types of cancers, including melanoma. In this in vitro study we tried to reveal the anticancer properties of CBD in malignant melanoma cell lines (SK-MEL 28, A375, FM55P and FM55M2) administered alone, as well as in combination with mitoxantrone (MTX) or cisplatin (CDDP). The effects of CBD on the viability of melanoma cells were measured by the MTT assay; cytotoxicity was determined in the LDH test and...