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.
https://www.cannabisclinicians.org/wp-content/uploads/2020/06/scc_logo-long-R-2-1.png00Michelle Smithhttps://www.cannabisclinicians.org/wp-content/uploads/2020/06/scc_logo-long-R-2-1.pngMichelle Smith2023-10-18 04:22:502023-10-18 04:22:50Cell death induction and intracellular vesicle formation in human colorectal cancer cells treated with Δ9 -Tetrahydrocannabinol
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.
https://www.cannabisclinicians.org/wp-content/uploads/2020/06/scc_logo-long-R-2-1.png00Michelle Smithhttps://www.cannabisclinicians.org/wp-content/uploads/2020/06/scc_logo-long-R-2-1.pngMichelle Smith2023-10-12 14:49:382023-10-12 14:49:38Anti-proliferative effect of Cannabidiol in Prostate cancer cell PC3 is mediated by apoptotic cell death, NFκB activation, increased oxidative stress, and lower reduced glutathione status
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.
https://www.cannabisclinicians.org/wp-content/uploads/2020/06/scc_logo-long-R-2-1.png00Michelle Smithhttps://www.cannabisclinicians.org/wp-content/uploads/2020/06/scc_logo-long-R-2-1.pngMichelle Smith2023-09-16 11:18:482023-09-16 11:18:48Cannabidiol alters mitochondrial bioenergetics via VDAC1 and triggers cell death in hormone-refractory prostate cancer
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.
https://www.cannabisclinicians.org/wp-content/uploads/2020/06/scc_logo-long-R-2-1.png00Michelle Smithhttps://www.cannabisclinicians.org/wp-content/uploads/2020/06/scc_logo-long-R-2-1.pngMichelle Smith2023-09-16 11:12:232023-09-16 11:12:23Cannabidiol Inhibits the Proliferation and Invasiveness of Prostate Cancer Cells
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.
https://www.cannabisclinicians.org/wp-content/uploads/2020/06/scc_logo-long-R-2-1.png00Michelle Smithhttps://www.cannabisclinicians.org/wp-content/uploads/2020/06/scc_logo-long-R-2-1.pngMichelle Smith2023-09-16 11:06:552023-09-16 11:07:11The clinical and pathological significance of increased expression of the cannabinoid receptors CB-1R and CB-2R in patients with papillary thyroid carcinomas compared to benign thyroid lesions
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.
https://www.cannabisclinicians.org/wp-content/uploads/2020/06/scc_logo-long-R-2-1.png00Michelle Smithhttps://www.cannabisclinicians.org/wp-content/uploads/2020/06/scc_logo-long-R-2-1.pngMichelle Smith2023-09-06 04:32:562023-09-06 04:32:56Could cannabinoids provide a new hope for ovarian cancer patients?
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.
https://www.cannabisclinicians.org/wp-content/uploads/2020/06/scc_logo-long-R-2-1.png00Michelle Smithhttps://www.cannabisclinicians.org/wp-content/uploads/2020/06/scc_logo-long-R-2-1.pngMichelle Smith2023-08-19 11:27:512023-08-19 11:27:51Single-cell analyses reveal cannabidiol rewires tumor microenvironment via inhibiting alternative activation of macrophage and synergizes with anti-PD-1 in colon cancer
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.
https://www.cannabisclinicians.org/wp-content/uploads/2020/06/scc_logo-long-R-2-1.png00Michelle Smithhttps://www.cannabisclinicians.org/wp-content/uploads/2020/06/scc_logo-long-R-2-1.pngMichelle Smith2023-08-12 12:06:192023-08-12 12:06:19Cannabinoids in the treatment of cancer anorexia and cachexia: where have we been, where are we going?
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.
https://www.cannabisclinicians.org/wp-content/uploads/2020/06/scc_logo-long-R-2-1.png00Michelle Smithhttps://www.cannabisclinicians.org/wp-content/uploads/2020/06/scc_logo-long-R-2-1.pngMichelle Smith2023-08-05 09:20:372023-08-05 09:20:37Could cannabinoids provide a new hope for ovarian cancer patients?
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
https://www.cannabisclinicians.org/wp-content/uploads/2020/06/scc_logo-long-R-2-1.png00Michelle Smithhttps://www.cannabisclinicians.org/wp-content/uploads/2020/06/scc_logo-long-R-2-1.pngMichelle Smith2023-07-15 19:10:252023-07-15 19:10:25Cannabis sativa demonstrates anti-hepatocellular carcinoma potentials in animal model: in silico and in vivo studies of the involvement of Akt
In 1991 the U.S. Congress mandated that the National Institutes of Health (NIH) form the Office of Alternative Medicine to study alternative medical therapies, especially in oncology care. Shortly after, the National Cancer Institute (NCI) created its own division of complementary and alternative medicine (Office of Complementary and Alternative Medicine). At the genesis of the field 30 years ago, what were we hoping to see accomplished by now? In this article we take a look back at milestones, shortfalls and future directions. Exciting opportunities exist to direct our established subspeciality’s future directions and we have made valuable advances the field of integrative oncology over the last 30 years: 1, IV high dose ascorbate has clinical research-based applications when used concurrently with some chemotherapeutic agents. 2. Whole body, extracorporeal and locoregional hyperthermia are being applied in treating solid tumors, including brain tumors. 3. PDL-1 tumor microenvironment testing and PDL-1 inhibitor immunotherapies have surprisingly excellent outcomes in a subgroup of cancer patients. 4. Tumor DNA sequencing (resected tumor and circulating tumor DNA in blood) has led to personalized precision targeted treatments. 5. Glucose metabolism’s role in cancer progression is better understood and better therapies are available (e.g., intermittent fasting, metformin). 6. Medical cannabis has a larger role in treating chemotherapy-related side effects and shows promise for anti-proliferative effects.
https://www.cannabisclinicians.org/wp-content/uploads/2020/06/scc_logo-long-R-2-1.png00Michelle Smithhttps://www.cannabisclinicians.org/wp-content/uploads/2020/06/scc_logo-long-R-2-1.pngMichelle Smith2023-06-17 14:25:342023-06-17 14:25:34Integrative Oncology’s 30-Year Anniversary: What Have We Achieved? A North American Naturopathic Oncology Perspective
An estimated 60% of melanoma patients develop melanoma brain metastases (MBMs). However, the molecular factors that govern the growth of MBMs are still unknown. The excitatory neurotransmitter glutamate has been shown to control the proliferation of various types of cancer cells within the brain parenchyma, but the cellular sources and molecular mechanisms involved in this process remain unclear. By their well-known role in inhibiting synaptic glutamate release, cannabinoid CB1 receptors (CB1Rs) located on glutamatergic nerve terminals are conceivably well-positioned to control the growth of MBMs. In silico data mining in cancer-genome atlases and in vitro studies with melanoma cell lines supported that a glutamate-NMDA receptor axis drives melanoma cell proliferation. Strikingly, grafting melanoma cells into the brain of mice lacking CB1Rs selectively in glutamatergic neurons increased tumour size and concomitantly activated NMDA receptors on tumour cells. Altogether, our findings reveal an unprecedented role of neuronal CB1Rs in controlling MBMs.
