Chemotherapy-induced peripheral neuropathy (CIPN) is experienced by 37–84% of patients during and/or after end-of-treatment and often results in discontinuation of anti-neoplastic treatment and impairment of health-related quality of life. Cannabidiol (CBD) has shown preventive effects in CIPN animal models without compromising chemotherapy efficacy.
Cannabis roots have been used in folk medicine for millennia and as nutrient storage systems, contain compounds that may have medicinal value. Despite this, cannabis roots have generally received little attention compared to cannabis flowers, leaves and seeds and were for a long time considered just a waste product. In this paper, for the first time, the extracts of dried roots and in- florescences of Cannabis sativa L. cv Eletta Campana, were chemically investigated in order to compare their metabolite content. The obtained results highlighted a profile rich in fatty acids in the roots and cannabinoids in the inflorescences. Other components such as monoterpenes, sesquiterpenes, diterpenes and triterpenes were also detected. The extracts were also evaluated in terms of cytotoxic activity by using a panel of cancer cell lines derived from different histotypes including melanoma (A375, M14), colon (HCT116, HT29), breast (MDAMB231, MCF7) and non- small cell lung cancer (H1299, A549). Although both extracts significantly reduced the cancer cell viability, the inflorescence extract was more potent. Furthermore, the latter induced a comparable response in all tested cancer cell lines, while melanoma and non-small cell lung cancer were the most sensitive histotypes to the root extract treatment.
Δ9-Tetrahydrocannabinol (Δ9-THC) is a principal psychoactive extract of Cannabis sativa and has been traditionally used as palliative medicine for neuropathic pain. Cannabidiol (CBD), an extract of hemp species, has recently attracted increased attention as a cancer treatment, but Δ9-THC is also requiring explored pharmacological application. This study evaluated the pharmacological effects of Δ9-THC in two human colorectal cancer cell lines. We inves-tigated whether Δ9-THC treatment induces cell death in human colorectal cancer cells.
Prostate cancer is the second most frequent cancer diagnosed in men in the world today. Almost all prostate cancers are adenocarcinomas and develop from gland cells. We used the PC3 prostate cancer cell line, which is well studied and derived from a bone metastasis of a grade IV prostatic adenocarcinoma. Cannabidiol (CBD), a major non-psychoactive constituent of cannabis, is a cannabinoid with anti-tumor properties but its effects on prostate cancer cells are not studied in detail. Here, we found cannabidiol decreased prostate cancer cell (PC3) viability up to 37.25% and induced apoptotic cell death in a time and dose-dependent manner. We found that CBD activated the caspases 3/7 pathways and increased DNA fragmentation. Furthermore, we observed an increase of pro-apoptotic genes Bax, an increased level of reactive oxygen species, lower reduced glutathione level, and altered mitochondrial potential in response to CBD treatment leading to lower cellular ATP. Overall, our results suggest that CBD may be effective against prostate cancer cells.
In spite of the huge advancements in both diagnosis and interventions, hormone refractory prostate cancer (HRPC) remains a major hurdle in prostate cancer (PCa). Metabolic reprogramming plays a key role in PCa oncogenesis and resistance. However, the dynamics between metabolism and oncogenesis are not fully understood. Here, we demonstrate that two multi-target natural products, cannabidiol (CBD) and cannabigerol (CBG), suppress HRPC development in the TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model by reprogramming metabolic and oncogenic signaling. Mechanistically, CBD increases glycolytic capacity and inhibits oxidative phosphorylation in enzalutamide-resistant HRPC cells. This action of CBD originates from its effect on metabolic plasticity via modulation of VDAC1 and hexokinase II (HKII) coupling on the outer mitochondrial membrane, which leads to strong shifts of mitochondrial functions and oncogenic signaling pathways. The effect of CBG on enzalutamide-resistant HRPC cells was less pronounced than CBD and only partially attributable to its action on mitochondria. However, when optimally combined, these two cannabinoids exhibited strong anti-tumor effects in TRAMP mice, even when these had become refractory to enzalutamide, thus pointing to their therapeutical potential against PCa.
Prostate cancer is the fifth leading cause of cancer death in men, responsible for over 375,000 deaths in 2020. Novel therapeutic strategies are needed to improve outcomes. Cannabinoids, chemical components of the cannabis plant, are a possible solution. Preclinical evidence demonstrates that cannabinoids can modulate several cancer hallmarks of many tumor types. However, the therapeutic potential of cannabinoids in prostate cancer has not yet been fully explored. The aim of this study was to investigate the antiproliferative and anti-invasive properties of cannabidiol (CBD) in prostate cancer cells in vitro. CBD inhibited cell viability and proliferation, accompanied by reduced expression of key cell cycle proteins, specifically cyclin D3 and cyclin-dependent kinases CDK2, CDK4, and CDK1, and inhibition of AKT phosphorylation. The effects of CBD on cell viability were not blocked by cannabinoid receptor antagonists, a transient receptor potential vanilloid 1 (TRPV1) channel blocker, or an agonist of the G-protein-coupled receptor GPR55, suggesting that CBD acts independently of these targets in prostate cancer cells. Furthermore, CBD reduced the invasiveness of highly metastatic PC-3 cells and increased protein expression of E-cadherin. The ability of CBD to inhibit prostate cancer cell proliferation and invasiveness suggests that CBD may have potential as a future chemotherapeutic agent.
Phytocannabinoids have been shown to inhibit the aggregation and neurotoxicity of the neurotoxic Alzheimer’s disease protein beta amyloid (Aβ). We characterised the capacity of six phytocannabinoids: cannabichromene, cannabigerol, cannabinol, cannabidivarin, cannabidiol and Δ9-tetrahydrocannabinol, to disrupt Aβ aggregation and protect against Aβ-evoked neurotoxicity in PC12 cells. Neuroprotection against lipid peroxidation and Aβ-induced cytotoxicity was assessed using the MTT assay. Transmission electron microscopy was used to visualise phytocannabinoid effects on Aβ aggregation and fluorescence microscopy, with morphometrics and principal component analysis to assess PC12 cell morphology.
It is known that gynecological cancers remain a worldwide problem and as shown by the statistics, there is a need for new gynecological cancer treatments. Cannabinoids, the pharmacologically active compounds of the Cannabis sativa plant, have been used for many centuries by individuals as a symptomatic treatment to alleviate pain, nausea, vomiting, and to help stimulate appetite. Research has revealed that cannabinoids also exert anti-cancer activity such as anti-proliferative and pro-apoptotic effects through a variety of mechanisms. There is significant value in the development of these compounds as anti-cancer therapies in clinical practice as they do not produce the typical toxic side effects that exist with conventional therapies and recent clinical trials have shown their great tolerability by patients at high doses.
Physicians’ ability to guide their patients on the use of medical cannabis can vary widely and is often shaped by their training, experiences, and the regulations and policies of their state. The goal of this qualitative study is to understand how prepared physicians are to certify and advise their patients to use medical cannabis. A secondary goal is to explore how physicians integrate certification into their clinical practices, and what factors shape their decisions and behaviors around certification.Using semi-structured interviews with 24 physicians authorized to certify patients to use medical cannabis in Pennsylvania, a state with a medical access only program, we explored how physi- cians are trained and set up their practices. Interviews were analyzed using a blend of directed and conventional, and summative content analysis.
Cachexia-anorexia cancer syndrome remains an unmet clinical need with a dearth of treatment and no standard of care. Acting through the endocannabinoid system, cannabinoids are one potential cancer cachexia treatment. Herein the potential mechanisms for cannabinoids for cancer cachexia are discussed as are previous and ongoing clinical trials.
It is known that gynecological cancers remain a worldwide problem and as shown by the statistics, there is a need for new gynecological cancer treatments. Cannabinoids, the pharmacologically active compounds of the Cannabis sativa plant, have been used for many centuries by individuals as a symptomatic treatment to alleviate pain, nausea, vomiting, and to help stimulate appetite. Research has revealed that cannabinoids also exert anti-cancer activity such as anti-proliferative and pro-apoptotic effects through a variety of mechanisms. There is significant value in the development of these com- pounds as anti-cancer therapies in clinical practice as they do not produce the typi- cal toxic side effects that exist with conventional therapies and recent clinical trials have shown their great tolerability by patients at high doses. Cannabinoids can induce psychoactive effects that could limit their progression. Therefore, non-psychoactive cannabinoids are attracting pharmacological interest due to their inability to produce psychological effects. Recent studies have focussed on non-psychoactive cannabi- noids in ovarian cancer and have revealed promising pre-clinical results that indicate that these compounds may have potential benefits in the treatment of these cancers. However, there are still unanswered questions and research gaps that need to be addressed. This review summarizes the current understanding of this topic and iden- tifies the current gaps in knowledge that provide a useful direction for future work.
Targeting protein kinase B (Akt) and its downstream signaling proteins are promising options in designing novel and potent drug candidates against hepatocellular carcinoma (HCC). The present study explores the anti-HCC potentials of Cannabis sativa (C. sativa) extract via the involvement of Akt using both in silico and in vivo animal models of HCC approaches.
Phytoconstituents of C. sativa extract obtained from Gas Chromatography Mass-spectrometry (GCSM) were docked into the catalytic domain of Akt-2. The Diethylnitrosamine (DEN) model of HCC was treated with C. sativa extract. The effects of C. sativa extract treatments on DEN model of hepatocellular carcinoma were assessed by One-way analysis of variance (ANOVA) of the treated and untreated groups