Anti-Cancer Activity of Cannabis sativa Phytocannabinoids: Molecular Mechanisms and Potential in the Fight against Ovarian Cancer and Stem Cells

Posted on September 10, 2022 by David

“Ovarian cancer (OC) is the most lethal gynecological malignancy, with about 70% of cases diagnosed only at an advanced stage.

Cannabis sativa, which produces more than 150 phytocannabinoids, is used worldwide to alleviate numerous symptoms associated with various medical conditions. Recently, studies across a range of cancer types have demonstrated that the phytocannabinoids Δ⁹-trans-tetrahydrocannabinol (THC) and cannabidiol (CBD) have anti-cancer activity in vitro and in vivo, but also the potential to increase other drugs’ adverse effects.

THC and CBD act via several different biological and signaling pathways, including receptor-dependent and receptor-independent pathways. However, very few studies have examined the effectiveness of cannabis compounds against OC. Moreover, little is known about the effectiveness of cannabis compounds against cancer stem cells (CSCs) in general and OC stem cells (OCSCs) in particular. CSCs have been implicated in tumor initiation, progression, and invasion, as well as tumor recurrence, metastasis, and drug resistance. Several hallmarks and concepts describe CSCs. OCSCs, too, are characterized by several markers and specific drug-resistance mechanisms.

While there is no peer-reviewed information regarding the effect of cannabis and cannabis compounds on OCSC viability or development, cannabis compounds have been shown to affect genetic pathways and biological processes related to CSCs and OCSCs. Based on evidence from other cancer-type studies, the use of phytocannabinoid-based treatments to disrupt CSC homeostasis is suggested as a potential intervention to prevent chemotherapy resistance. The potential benefits of the combination of chemotherapy with phytocannabinoid treatment should be examined in ovarian cancer patients.”

https://pubmed.ncbi.nlm.nih.gov/36077833/

“Ovarian cancer is the most lethal gynecological malignancy. Cancer stem cells have been implicated in tumor initiation, progression, and invasion, as well as tumor recurrence, metastasis, and drug resistance. Cannabis is used worldwide to alleviate numerous symptoms associated with various medical conditions. Phytocannabinoids, produced by cannabis, were shown to have anti-cancer activity in cell lines and animal models, but also the potential to increase other drugs’ adverse effects. Yet, very few studies have examined the effectiveness of cannabis compounds against ovarian cancer. Cannabis compounds have been shown to affect genetic pathways and biological processes related to development of ovarian cancer stem cells. Phytocannabinoid-based treatments might be used to disrupt cancer stem cell homeostasis and thereby to prevent chemotherapy resistance. The potential benefits of the combination of chemotherapy with phytocannabinoid treatment could be examined in ovarian cancer patients.”

https://www.mdpi.com/2072-6694/14/17/4299/htm

Practical Considerations for the Use of Cannabis in Cancer Pain Management-What a Medical Oncologist Should Know

Posted on September 10, 2022 by David

“Pain is a highly debilitating emotional and sensory experience that significantly affects quality of life (QoL). Numerous chronic conditions, including cancer, are associated with chronic pain. In the setting of malignancy, pain can be a consequence of the tumor itself or of life-saving interventions, including surgery, chemotherapy, and radiotherapy. Despite significant pharmacological advances and awareness campaigns, pain remains undertreated in one-third of patients. To date, opioids have been the mainstay of cancer pain management. The problematic side effects and unsatisfactory pain relief of opioids have revived patients’ and physicians’ interest in finding new solutions, including cannabis and cannabinoids. The medical use of cannabis has been prohibited for decades, and it remains in Schedule 1 of the Misuse of Drugs Regulations. Currently, the legal context for its usage has become more permissive. Various preclinical and observational studies have aimed to prove that cannabinoids could be effective in cancer pain management. However, their clinical utility must be further supported by high-quality clinical trials.”

https://pubmed.ncbi.nlm.nih.gov/36078963/

https://www.mdpi.com/2077-0383/11/17/5036/htm

Experience With Medical Marijuana for Cancer Patients in the Palliative Setting

Posted on August 29, 2022 by David

Cureus Competition Winners Announced - Synaptive Medical

“Objectives: Medical marijuana is a symptom treatment option for palliative cancer patients; however, its useful applications remain limited. The goals of this study were to review the characteristics of patients who received medical marijuana under our ambulatory palliative care program and to determine barriers to access and use of medical marijuana in this population.

Methods: This study was a retrospective analysis of patients who were enrolled in the medical marijuana registry through the ambulatory palliative care department at Upstate Cancer Center. Data from June 2017 to June 2020 were analyzed. Patients were included if they had a diagnosis of cancer, were certified by a qualified practitioner in the New York Medical Marijuana Program, and received care at Upstate Medical University. Patients were excluded if no marijuana certificate was found or if they transferred care.

Results: The study population was 184 patients. Ninety-three patients (51.5%) received at least one prescription from a New York licensed marijuana dispensary while 72 (39.13%) were certified but never obtained any medical marijuana. For patients who took at least one dose of medical marijuana, 48.14% experienced an improvement in pain, 44.95% used fewer opioids, and 85.11% had an improvement in at least one symptom. Adverse effects were low at 3.72%.

Conclusion: Medical marijuana has an important role in the palliation of symptoms in advanced cancers with few adverse effects. There are still many barriers to effective use. More prospective research is needed to optimize delivery and dosing.”

https://pubmed.ncbi.nlm.nih.gov/35915672/

“Medical marijuana appears to have an important role in the palliation of symptoms in advanced cancers with few adverse effects although not all patients certified for use, go on to obtain it. There are many remaining barriers to effective use including financial toxicity and end-of-life care, introducing this so late in life that the benefit is limited.”

https://www.cureus.com/articles/102316-experience-with-medical-marijuana-for-cancer-patients-in-the-palliative-setting

Cannabinoid Cancer Biology and Prevention

Posted on August 27, 2022 by David

“Plant-based, synthetic, and endogenous cannabinoids have been shown to control a diverse array of biological processes, including regulation of cell fate across cancers. Their promise as broad-based antitumor agents in preclinical models has led to the initiation of pilot clinical trials. Session 5 of the National Cancer Institute’s Cannabis, Cannabinoids and Cancer Research Symposium provides an overview of this research topic.

Overall, the presentations highlight cannabinoid signal transduction and specific molecular mechanisms underlying cannabinoid antitumor activity. They also demonstrate the broad-based antitumor activity of the plant-based, synthetic, and endogenous cannabinoid compounds. Importantly, evidence is presented demonstrating when cannabinoids may be contraindicated as a treatment for cancer, as in the case of human papilloma virus-meditated oropharynx cancer or potentially other p38 MAPK pathway-driven cancers.

Finally, it is discussed that a key to advancing cannabinoids into the clinic is to conduct well-designed, large-scale clinical trials to determine whether cannabinoids are effective antitumor agents in cancer patients.”

https://pubmed.ncbi.nlm.nih.gov/34850900/

“These sessions present multiple lines of preclinical evidence supporting that the cannabinoids THC and CBD act as broad-based antitumor agents controlling many aspects of cancer progression, including cell proliferation, apoptosis, invasion, metastasis, and immune surveillance. “

https://academic.oup.com/jncimono/article/2021/58/99/6446216?login=false

Analysis of Potential Anti-Cancer Effects of Cannabinol and Cannabidiol using HCC1806 and HEK293 Cell Lines

Posted on August 27, 2022 by David

“Humans produce endocannabinoids that act as neuromodulators in the endocannabinoid system. They bind to Gαi protein-coupled cannabinoid receptors to control the release of many neurotransmitters. Cannabinoids receptor 1 (CB1) mediates psychoactive effects through its location mostly in the central nervous system while Cannabinoid receptor 2 (CB2) regulates various immune responses through its location in peripheral tissues.

The endocannabinoid system has been used as a molecular target by research to treat diseases such as multiple sclerosis, cardiovascular disorders, obesity and inflammatory pain. Thus, the endocannabinoid system is a potential molecular target to treat cancer. With the proposed legalization of recreational marijuana and with growing number of patients using cannabis for medicinal purpose, there is an urgent need to provide data on potential medicinal value of cannabis and cannabinoids.

The Cannabis Sativa plant naturally synthesizes numerous different cannabinoids of which (CBN) and cannabidiol (CBD) have promising properties in cancer treatment. CBD is a phytocannabinoid known for its anticonvulsant and anti-nausea properties. Previous research suggests that CBD can target breast cancer cells while preserving normal cells. CBN is another phyotocannabinoid with anti-inflammatory properties that can potentially aid to reduce inflammation resulting from cancer.

This study aims to determine if CBN and CBD have an effect on cancer cells and normal cells. We hypothesize that we may observe an increase in apoptosis of cancer cells treated with the two compounds but no effect or perhaps even a slight increase in normal cell growth. Preliminary data in lab suggests that these compounds have anti-cancer properties and we want to solidify this evidence through repetition of the experiment.”

https://journals.macewan.ca/ursca/article/view/1582

Hemp ( Cannabis sativa L., Kompolti cv.) and Hop ( Humulus lupulus L., Chinook cv.) Essential Oil and Hydrolate: HS-GC-MS Chemical Investigation and Apoptotic Activity Evaluation

Posted on August 26, 2022 by David

“In this study, essential oils (EOs) and hydrolates (Hys) from Italian hemp (Cannabis sativa L. Kompolti cv.) and hop (Humulus Lupulus L., Chinook cv.) supply chains were chemically characterized and tested to investigate their apoptotic potential for the first time. Headspace-Gas Chromatography-Mass Spectrometry (HS-GC-MS) techniques were performed to describe their volatile chemical profile, highlighting a composition rich in terpene derivatives such as monoterpenes and sesquiterpenes among which β-myrcene, limonene, β-caryophyllene and α-humulene were the main constituents of EOs; in contrast, linalool, cis–p-menth-2,8-dien-1-ol, terpinen-4-ol, α-terpineol, caryophyllene oxide, and τ-cadinol were found in the Hys.

The cytotoxicity activity on human leukemia cells (HL60), human neuroblastoma cells (SH-SY5Y), human metastatic adenocarcinoma breast cells (MCF7), human adenocarcinoma breast cells (MDA), and normal breast epithelial cell (MCF10A) for the EOs and Hys was studied by MTT assay and cytofluorimetric analysis and scanning and transmission electron microscopy were performed to define ultrastructural changes and the mechanism of cells death for HL 60 cells.

An induction of the apoptotic mechanism was evidenced for hemp and hop EOs after treatment with the corresponding EC₅₀ dose. In addition, TEM and SEM investigations revealed typical characteristics induced by the apoptotic pathway. Therefore, thanks to the integration of the applied methodologies with the used techniques, this work provides an overview on the metabolomic profile and the apoptotic potential of hemp and hop EOs and, for the first time, also of Hys.

The findings of this preliminary study confirm that the EOs and Hys from Cannabis and Humulus species are sources of bioactive molecules with multiple biological effects yet to be explored.”

https://pubmed.ncbi.nlm.nih.gov/36015124/

https://www.mdpi.com/1424-8247/15/8/976/htm

Evaluation of Sex Differences in the Potential of Δ 9-Tetrahydrocannabinol, Cannabidiol, Cannabidiolic Acid, and Oleoyl Alanine to Reduce Nausea-Induced Conditioned Gaping Reactions in Sprague-Dawley Rats

Posted on August 22, 2022 by David

View details for Cannabis and Cannabinoid Research cover image

“Introduction: Cancer patients report nausea as a side effect of their chemotherapy treatment. Using the pre-clinical rodent model of acute nausea-lithium chloride (LiCl)-induced conditioned gaping-our group has demonstrated that exogenous cannabinoids may have antinausea potential.

Materials and Methods: With the goal of evaluating the role of sex as a factor in pre-clinical research, we first compared the conditioned gaping reactions produced by varying doses of LiCl in male and female rats using the taste reactivity test (Experiment 1).

Results: LiCl produced dose-dependent conditioned gaping similarly in male and female rats with the highest dose (127.2 mg/kg) producing robust conditioned gaping, with this dose used in subsequent experiments. Next, we examined the antinausea potential of THC (Experiment 2), CBD (Experiment 3), cannabidiolic acid (CBDA; Experiment 4) and oleoyl alanine (OlAla; Experiment 5) in both male and female rats. THC, CBD, CBDA, and OlAla dose dependently reduced conditioned gaping in both male and female rats in a similar manner.

Conclusions: These results suggest that cannabinoids may be equally effective in treating nausea in both males and females.”

https://pubmed.ncbi.nlm.nih.gov/35984924/

https://www.liebertpub.com/doi/10.1089/can.2022.0158

Investigation of the Effects of the Endogenous Cannabinoid Anandamide on Luminal A Breast Cancer Cell Line MCF-7

Posted on August 22, 2022 by David

“The present study was carried out to investigate anti-tumoral effects of Anandamide (AEA) in luminal A breast cancer cell line MCF-7. Cell viability was measured by MTT assay and cell index was measured by xCelligence DP analyzer system. The Feulgen method was used to determine the mitotic index parameter, and the 3H-Thymidine method was used to determine the labeling index parameter. The apoptotic index parameter was determined using a fluorescent dye DAPI. The results of this study showed that 25 µM Anandamide concentration was the optimum concentration for MCF-7 cells. While this concentration decreased the proportion of cells in the mitotic phase and synthesis phase, it increased the proportion of apoptotic cells.”

https://pubmed.ncbi.nlm.nih.gov/35988272/

https://www.cellmolbiol.org/index.php/CMB/article/view/4374

γ-Terpinene complexed with β-cyclodextrin attenuates spinal neuroactivity in animals with cancer pain by Ca2+ channel block

Posted on August 19, 2022 by David

“Objectives: Considering that γ-terpinene (γ-TPN) is a monoterpene found in Cannabis oil, with high lipophilicity and limited pharmacokinetics, our objective was to evaluate whether its complexation in β-cyclodextrin (γ-TPN/β-CD) could improve its physicochemical properties and action on cancer pain, as well as verify the mechanisms of action involved.

Results: β-CD improved the physicochemical properties and prolonged the anti-hyperalgesic effect of γ-TPN. This compound also reduced the levels of IL-1β, TNF-α and iNOS in the tumour, and c-Fos protein in the spinal cord. In addition, it reduced Ca2+ current, presenting favourable chemical interactions with different voltage-dependent calcium channels.

Conclusion: These results indicate that the complexation of γ-TPN into β-CD increases its stability and time effect, reducing spinal neuroactivity and inflammation by blocking calcium channels.”

https://pubmed.ncbi.nlm.nih.gov/35976257/#affiliation-2

https://academic.oup.com/jpp/advance-article-abstract/doi/10.1093/jpp/rgac052/6670692?redirectedFrom=fulltext&login=false

Anticancer activity of Δ9-tetrahydrocannabinol and cannabinol in vitro and in human lung cancer xenograft

Posted on August 18, 2022 by David

“Objective: To investigate the effects of Δ⁹-tetrahydrocannabinol, the principal psychoactive compound of Cannabis sativa, and cannabinol, a Δ⁹-tetrahydrocannabinol degradative product, on human non-small cell lung cancer cells.
Methods: Δ⁹-Tetrahydrocannabinol and cannabinol were tested for anticancer activity in human non-small cell lung cancer (A549) cells. The effects on cell proliferation, apoptosis, and phosphorylation profiles were examined. The effects of Δ⁹-tetrahydrocannabinol and cannabinol on tumor growth were also investigated using a xenograft nude mouse model. Apoptosis and targeted phosphorylation were verified by immunohistochemistry.
Results: Δ⁹-Tetrahydrocannabinol and cannabinol significantly inhibited cell proliferation and increased the number of apoptotic cells in a concentration-dependent manner. The Δ⁹-tetrahydrocannabinol- and cannabinol-treated cells had lower levels of phosphorylated protein kinase B [AKT (S473)], glycogen synthase kinase 3 alpha/beta, and endothelial nitric oxide synthase compared to the controls. The study of xenograft mice revealed that tumors treated with 15 mg/kg Δ⁹-tetrahydrocannabinol or 40 mg/kg cannabinol were significantly smaller than those of the control mice. The tumor progression rates in mice treated with 15 mg/kg Δ⁹-tetrahydrocannabinol or 40 mg/kg cannabinol were significantly slower than in the control group.
Conclusions: These findings indicate that Δ⁹-tetrahydrocannabinol and cannabinol inhibit lung cancer cell growth by inhibiting AKT and its signaling pathways, which include glycogen synthase kinase 3 alpha/beta and endothelial nitric oxide synthase.”

https://journals.lww.com/aptb/fulltext/2022/12080/anticancer_activity_of__9_tetrahydrocannabinol_and.1.aspx

www.thctotalhealthcare.com

Category Archives: Cancer