Category Archives: Cancer

Effects of Cannabidiol (CBD) on Doxorubicin-Induced Anxiety and Depression-like Behaviors and mRNA Expression of Inflammatory Markers in Rats

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“Background: Post-treatment side effects of chemotherapy can include cognitive deficits commonly known as Chemo-brain. The treatment of patients with Doxorubicin (DOX), one of the most widely used chemotherapeutic drugs in the treatment of cancer, can induce depression, anxiety, and impaired cognitive function. Cannabidiol (CBD) is a non-psychoactive component of Cannabis sativa that has been identified as a possible therapeutic agent against many neurodegenerative disorders, including traumatic brain injury, spinal cord injury, Tau-protein-induced neurodegeneration, and neuropathic pain. Therefore, this study aimed to assess whether oral CBD administration could reduce DOX-induced anxiety and depression-like behaviors and alter the expression of mRNA associated with neuroinflammation. 

Methods: Female Long Evans Hooded rats received intraperitoneal injections of DOX (6 mg/kg) or the vehicle (0.9% saline) once a week for four weeks, followed by oral administration of CBD (10 mg/kg) three times a week for the same period. 

Results: CBD was significantly protective against DOX-induced anxiety and depression-like behaviors, as measured by several behavioral tests. Furthermore, CBD improved DOX-induced alterations in the gene expression of biomarkers of neuroinflammation in the hippocampus and prefrontal cortex. 

Conclusions: This provides insights into future studies on possible mechanisms by which DOX-induced cognitive dysfunction could be alleviated by CBD.”

https://pubmed.ncbi.nlm.nih.gov/39452013/

“In conclusion, this study demonstrated that the chronic, systemic administration of DOX impairs cognitive abilities in rats, increases anxiety and depression-like behaviors, and regulates the expression of genes involved in neuroinflammation. We found that CBD-treated rats had fewer anxiety and depression-like behaviors than rats treated with DOX alone.”

https://www.mdpi.com/2076-3425/14/10/999

In Vitro Antitumor Effect of Oils Rich in CBD and THC Cannabis Extract in Canine Prostate Carcinoma Cell Lines

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“Prostate cancer is one of the leading causes of cancer-related deaths worldwide, even when diagnosed at an early stage in humans and dogs. Dogs have a significant incidence of spontaneous prostate cancer, which is highly similar to human androgen-independent prostate cancer and represents a valuable model for comparative studies.

Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are the two main cannabinoids extracted from Cannabis sativa and have demonstrated antiproliferative and anti-invasive properties in different tumor types.

In this study, CBD or THC-rich extracts inhibited the proliferation of two canine prostatic carcinoma cell lines, PC1 and PC2, showing an IC50 of 3.43 and 3.57 μM for CBD rich extracts, and 4.90 and 4.48 μM THC rich extracts, respectively. Cell death was also observed with both Annexin V and Propidium iodide staining for the canine cell lines.

These results provide new information concerning the use of rich oil in canine PC and open a promising opportunity for further in vitro and in vivo studies to establish the mechanisms of action of these compounds using dogs as a natural model for prostatic carcinoma.”

https://pubmed.ncbi.nlm.nih.gov/39453093/

“Cannabidiol and Δ9-tetrahydrocannabinol are the two main components of Cannabis sativa and have been shown to have anti-cancer properties. In this study, extracts rich in cannabidiol or Δ9-tetrahydrocannabinol inhibited the growth of two canine prostate carcinoma cell lines. These results provide new information about the use of these natural compounds in canine models, which gives us the opportunity for further studies, both in the laboratory and in animals, to discover how these compounds act in the body, using dogs as a natural model for prostate carcinoma.”

https://www.mdpi.com/2306-7381/11/10/501

DNA damage and cell death in human oral squamous cell carcinoma cells: The potential biological effects of cannabidiol

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“Objective: The present study examined the in vitro effects on oral squamous cell carcinoma cells (HSC-3) of cannabidiol (CBD), the main chemical component of Cannabis, proposed as a novel adjuvant therapy in the treatment of cancers.

Design: Cell viability (MTT assay), morphology (SEM), apoptosis and cell cycle (flow cytometry), and DNA damage (phospho-γ-H2AX immunofluorescence) were evaluated. Cytotoxicity was evaluated with concentrations between 100 µM and 1 µM, and two concentrations were selected for subsequent analysis: 25 µM, as toxic dose, and 6.25 µM, as non-toxic.

Results: CBD caused a dose- and time-dependent reduction in viability of 64 %, 96 %, and 99 % with 25 µM, 50 µM and 100 µM, respectively, after 72 h (p < 0.001), cell cycle arrest in G0-G1 phase with increased apoptosis in particular at 72 h for 25 µM (p < 0.001), significant morphological alterations with 25 µM, still present even at 6.25 µM, and significantly increased cell damage considering a significant increase in the percentage of highly positive cells (5 phosphorylated γH2AX foci), which is around 29 % for 25 µM and 19 % for 6.25 µM after 24 h.

Conclusions: CBD inhibits oral cancer growth causing DNA damage. In general, induced cell cytotoxicity appears to be dose- and time-related. Doses of CBD ≥25 μM showed a high reduction in viability. CBD could possibly represent a new therapeutic molecule for its cytotoxic effects against oral squamous cell carcinoma. The mechanism involved in the suppressive effect caused by CBD needs further investigation.”

https://pubmed.ncbi.nlm.nih.gov/39426313/

“CBD represent a new therapeutic molecule against oral squamous cell carcinoma.”

https://www.sciencedirect.com/science/article/abs/pii/S0003996924002310?via%3Dihub

Exploring the Potential of Synthetic Cannabinoids: Modulation of Biological Activity of Normal and Cancerous Human Colon Epithelial Cells

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“Colorectal cancer (CRC) is a global problem. Oncology currently practices conventional methods of treating this carcinoma, including surgery, chemotherapy, and radiotherapy. Unfortunately, their efficacy is low; hence, the exploration of new therapies is critical.

Recently, many efforts have focused on developing safe and effective anticancer compounds. Some of them include cannabinoids.

In the present study, we obtained cannabinoids, such as cannabidiol (CBD), abnormal cannabigerol (abn-CBG), cannabichromene (CBC), and cannabicitran (CBT), by chemical synthesis and performed the biological evaluation of their activity on colon cancer cells. In this study, we analyzed the effects of selected cannabinoids on the lifespan and metabolic activity of normal colonic epithelial cells and cancer colon cells.

This study demonstrated that cannabinoids can induce apoptosis in cancer cells by modulating mitochondrial dehydrogenase activity and cellular membrane integrity. The tested cannabinoids also influenced cell cycle progression. We also investigated the antioxidant activity of cannabinoids and established a relationship between the type of cannabinoid and nitric oxide (NO) production in normal and cancerous colon cells.

To conclude, it seems that, due to their interesting properties, the cannabinoids studied may constitute an interesting target for further research aimed at their use in alternative or combined therapies for human colon cancer.”

https://pubmed.ncbi.nlm.nih.gov/39404380/

“It seems that, due to their interesting properties, the cannabinoids studied may constitute an interesting target for further research, aimed at their use in alternative or combined therapies for human colon cancer.”

https://www.mdpi.com/2073-4409/13/19/1616

Preparation of a nanoemulsion containing active ingredients of cannabis extract and its application for glioblastoma: in vitro and in vivo studies

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“Recently, the anti-tumor effects of cannabis extract on various cancers have attracted the attention of researchers.

Here, we report a nanoemulsion (NE) composition designed to enhance the delivery of two active components in cannabis extracts (∆9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD)) in an animal model of glioblastoma. The efficacy of the NE containing the two drugs (NED) was compared with the bulk drugs and carrier (NE without the drugs) using the C6 tumor model in rats. Hemocompatibility factors (RBC, MCV, MCH, MCHC, RDW, PPP, PT and PTT) were studied to determine the potential in vivo toxicity of NED. The optimized NED with mean ± SD diameter 29 ± 6 nm was obtained.

It was shown that by administering the drugs in the form of NED, the hemocompatibility increased. Cytotoxicity studies indicated that the NE without the active components (i.e. mixture of surfactants and oil) was the most cytotoxic group, while the bulk group had no toxicity. From the in vivo MRI and survival studies, the NED group had maximum efficacy (with ~4 times smaller tumor volume on day 7 of treatment, compared with the control. Also, survival time of the control, bulk drug, NE and NED were 9, 4, 12.5 and 51 days, respectively) with no important adverse effects.

In conclusion, the NE containing cannabis extract could be introduced as an effective treatment in reducing brain glioblastoma tumor progression.”

https://pubmed.ncbi.nlm.nih.gov/39375818/

“Based on our findings, the nanoemulsion model containing CBD and THC increased the antitumor effect of the drugs. This may be due to the role of nanoemulsions in improving drug delivery across the blood-brain barrier and improving blood compatibility during intravenous drug administration. However, this study is a primary investigation in the rat animal model, and future studies should consider further evaluation of toxicity and efficacy in larger animal populations.”

https://bmcpharmacoltoxicol.biomedcentral.com/articles/10.1186/s40360-024-00788-w

A new cannabigerol derivative, LE-127/2, induces autophagy mediated cell death in human cutaneous melanoma cells

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“Despite the targeted- and immunotherapies used in the past decade, survival rate among patients with metastatic melanoma remains low, therefore, melanoma is responsible for the majority of skin cancer-related deaths.

The ongoing investigation of natural antitumor agents, the nonpsychoactive cannabinoid, cannabigerol (CBG) found in Cannabis sativa is emerging as a promising candidate. CBG offers a potential therapeutic role in the treatment of melanoma demonstrating cell growth inhibition in some tumors. Its low water solubility and bioavailability hinder the potential effectiveness. To address these challenges, a modified CBG, namely LE-127/2 was synthesized by Mannich-type reaction.

The aim was to investigate the effect of this novel compound on cell proliferation as well as the mechanism of cell death with a particular focus on autophagy and apoptosis.

Human cutan melanoma cell lines, WM35, A2058 and WM3000 were utilized for the present study. Cell proliferation of the cells after the treatment with LE-127/2, parent CBG or vemurafenib was assessed by Cell Titer Blue Assay. Cells were treated with a 1.25-80 µM of the above-mentioned compounds, and it was found that at 20 μM of all drugs showed a comparable effective inhibition of cell proliferation, however, vemurafenib and CBG proved to be more effective than LE-127/2. In addition, clonogenic cell survival assays were performed to examine the inhibitory effect of LE-127/2 on the colony formation ability of melanoma cell lines.

Cells treated with 20 µM of LE-127/2 for 14 days showed about a 50% suppression of clonogenic cell survival. LE-127/2 exerted the most intensive inhibition on A2058 cell colonies. Furthermore, notably, LDH cytotoxicity assay performed on HaCaT cell line, proved LE-127/2 to be cytotoxic only at higher concentration, such as 80 μM, while the parent CBG was cytotoxic at concentration as low as 5 μM, suggesting that the new CBG derivative as a drug candidate may be applied in human pharmacotherapy without causing a substantial damage in intact epidermal cells. Analysis of protein expression revealed the impact of LE-127/2 on the expression of basic proteins (LC-3, Beclin-1 and p62) involved in the process of autophagy in the three different melanoma cell lines studied. Elevated expression of these proteins was detected as a result of LE-127/2 (20 µM) treatment. LE-127/2 also induced the expression of some proteins involved in apoptosis, and it is particularly noteworthy the increased level of cleaved PARP.

Based on the results obtained, it can be concluded that LE-127/2 induced autophagy could lead to the inhibition of cell proliferation and death in melanoma cells.”

https://pubmed.ncbi.nlm.nih.gov/39357769/

https://www.sciencedirect.com/science/article/pii/S0928098724002331?via%3Dihub

Molecular Targets of Minor Cannabinoids in Breast Cancer: In Silico and In Vitro Studies

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“Background: Breast cancer therapy has been facing remarkable changes. Classic treatments are now combined with other therapies to improve efficacy and surpass resistance. Indeed, the emergence of resistance demands the development of novel therapeutic approaches. Due to key estrogen signaling, estrogen receptor-positive (ER+) breast cancer treatment has always been focused on aromatase inhibition and ER modulation. Lately, the effects of phytocannabinoids, mainly Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), have been evaluated in different cancers, including breast. However, Cannabis sativa contains more than 120 phytocannabinoids less researched and understood.

Methods: Here, we evaluated, both in silico and in vitro, the ability of 129 phytocannabinoids to modulate important molecular targets in ER+ breast cancer: aromatase, ER, and androgen receptor (AR).

Results: In silico results suggested that some cannabinoids may inhibit aromatase and act as ERα antagonists. Nine selected cannabinoids showed, in vitro, potential to act either as ER antagonists with inverse agonist properties, or as ER agonists. Moreover, these cannabinoids were considered as weak aromatase inhibitors and AR antagonists with inverse agonist action.

Conclusions: Overall, we present, for the first time, a comprehensive analysis of the actions of the phytocannabinoids in targets of ER+ breast tumors, pointing out their therapeutic potential in cancer and in other diseases.”

https://pubmed.ncbi.nlm.nih.gov/39338407/

“From the best of our knowledge, this is the first study exploring the molecular targets of minor cannabinoids and, together with previous studies, it reinforces the importance and therapeutic potential of cannabinoids in breast cancer, paving the way for novel and alternative therapeutic approaches and highlighting the medicinal potential of Cannabis.”

https://www.mdpi.com/1424-8247/17/9/1245

Exploring the therapeutic potential of cannabinoids in cancer by modulating signaling pathways and addressing clinical challenges

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“For centuries, cannabinoids have been utilized for their medicinal properties, particularly in Asian and South-Asian countries. Cannabis plants, known for their psychoactive and non-psychoactive potential, were historically used for spiritual and remedial healing. However, as cannabis became predominantly a recreational drug, it faced prohibition.

Recently, the therapeutic potential of cannabinoids has sparked renewed research interest, extending their use to various medical conditions, including cancer. This review aims to highlight current data on the involvement of cannabinoids in cancer signaling pathways, emphasizing their potential in cancer therapy and the need for further investigation into the underlying mechanisms.

A comprehensive literature review was conducted using databases such as PubMed/MedLine, Google Scholar, Web of Science, Scopus, and Embase. The search focused on peer-reviewed articles, review articles, and clinical trials discussing the anticancer properties of cannabinoids. Inclusion criteria included studies in English on the mechanisms of action and clinical efficacy of cannabinoids in cancer.

Cannabinoids, including Δ9-THC, CBD, and CBG, exhibit significant anticancer activities such as apoptosis induction, autophagy stimulation, cell cycle arrest, anti-proliferation, anti-angiogenesis, and metastasis inhibition. Clinical trials have demonstrated cannabinoids’ efficacy in tumor regression and health improvement in palliative care. However, challenges such as variability in cannabinoid composition, psychoactive effects, regulatory barriers, and lack of standardized dosing remain.

Cannabinoids show promising potential as anticancer agents through various mechanisms. Further large-scale, randomized controlled trials are essential to validate these findings and establish standardized therapeutic protocols. Future research should focus on elucidating detailed mechanisms, optimizing dosing, and exploring cannabinoids as primary chemotherapeutic agents.”

https://pubmed.ncbi.nlm.nih.gov/39331301/

https://link.springer.com/article/10.1007/s12672-024-01356-8

“Cannabis Compounds Show ‘Promising Potential As Anticancer Agents’”

https://www.forbes.com/sites/ajherrington/2024/10/08/cannabis-compounds-show-promising-potential-as-anti-cancer-agents/

The Efficacy of Cannabis in Oncology Patient Care and Its Anti-Tumor Effects

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“As the legalization of medical cannabis expands across several countries, interest in its potential advantages among cancer patients and caregivers is burgeoning. However, patients seeking to integrate cannabis into their treatment often encounter frustration when their oncologists lack adequate information to offer guidance. This knowledge gap is exacerbated by the scarcity of published literature on the benefits of medical cannabis, leaving oncologists reliant on evidence-based data disheartened. This comprehensive narrative article, tailored for both clinicians and patients, endeavors to bridge these informational voids. It synthesizes cannabis history, pharmacology, and physiology and focuses on addressing various symptoms prevalent in cancer care, including insomnia, nausea and vomiting, appetite issues, pain management, and potential anti-cancer effects. Furthermore, by delving into the potential mechanisms of action and exploring their relevance in cancer treatment, this article aims to shed light on the potential benefits and effects of cannabis in oncology.”

https://pubmed.ncbi.nlm.nih.gov/39199679/

“Cancer is a major disease and a leading cause of death worldwide. Improving treatment and management strategies for cancer is critical. This article explores cannabis and its pharmacological properties as a promising tool in cancer care, especially in easing symptoms like appetite loss, pain, nausea, vomiting, and insomnia. Moreover, it examines the anti-tumor properties of cannabis, highlighting that, although some evidence suggests benefits, more research is necessary to confirm these effects. The article addresses the evidence concerning the clinical challenges of using cannabis, such as its psychoactive effects, and potential side effects. The article aims to clarify the current understanding of cannabis use in cancer care, helping healthcare professionals and patients make better-informed decisions and improve treatment outcomes.”

https://www.mdpi.com/2072-6694/16/16/2909

Cannabinoid combination targets NOTCH1-mutated T-cell acute lymphoblastic leukemia through the integrated stress response pathway

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“In T-cell acute lymphoblastic leukemia (T-ALL), more than 50% of cases display autoactivation of Notch1 signaling, leading to oncogenic transformation.

We have previously identified a specific chemovar of Cannabis that induces apoptosis by preventing Notch1 maturation in leukemia cells. Here, we isolated three cannabinoids from this chemovar that synergistically mimic the effects of the whole extract. Two were previously known, cannabidiol (CBD) and cannabidivarin (CBDV), whereas the third cannabinoid, which we termed 331-18A, was identified and fully characterized in this study.

We demonstrated that these cannabinoids act through cannabinoid receptor type 2 and TRPV1 to activate the integrated stress response pathway by depleting intracellular Ca2+. This is followed by increased mRNA and protein expression of ATF4, CHOP, and CHAC1, which is hindered by inhibiting the upstream initiation factor eIF2α. The increased abundance of CHAC1 prevents Notch1 maturation, thereby reducing the levels of the active Notch1 intracellular domain, and consequently decreasing cell viability and increasing apoptosis.

Treatment with the three isolated molecules resulted in reduced tumor size and weight in vivo and slowed leukemia progression in mice models. Altogether, this study elucidated the mechanism of action of three distinct cannabinoids in modulating the Notch1 pathway, and constitutes an important step in the establishment of a new therapy for treating NOTCH1-mutated diseases and cancers such as T-ALL.”

https://pubmed.ncbi.nlm.nih.gov/39258755/

https://elifesciences.org/articles/90854