Why we think it’s important
The article discussed in this blog highlights the therapeutic potential of minor phytocannabinoids, which could offer new avenues for medical treatments beyond the well-known effects of THC and CBD. Understanding these compounds could lead to the development of novel therapies for conditions such as inflammation, pain, neurological disorders, and cancer.
Introduction
Multiple myeloma (MM) is a challenging blood cancer characterized by the uncontrolled growth of clonal plasma cells in the bone marrow. This disease often leads to severe bone complications due to the infiltration of myeloma cells into the bone marrow, where they stimulate osteoclast activity, resulting in excessive bone resorption. Despite advances in treatment, MM remains incurable, with patients frequently relapsing and becoming resistant to various drug classes.
Cannabinoids, compounds found in cannabis, are widely recognized for their palliative benefits in cancer patients, such as pain relief, anti-nausea effects, and mood stabilization. Recent studies have also suggested that cannabinoids possess direct anticancer properties in various cancer models. However, there is limited research on the effects of cannabinoids specifically on MM, especially minor phytocannabinoids like cannabigerol (CBG), cannabichromene (CBC), cannabinol (CBN), and cannabidivarin (CBDV).
Minor phytocannabinoids are naturally occurring chemical compounds found in the cannabis plant, similar to the more well-known cannabinoids like THC (tetrahydrocannabinol) and CBD (cannabidiol). Unlike THC and CBD, which are considered major cannabinoids due to their abundance and significant presence in cannabis, minor phytocannabinoids are found in much smaller quantities. These minor cannabinoids may offer new therapeutic avenues for MM due to their potential anticancer effects and ability to alleviate bone disease.
Key Findings
A recent study explored the anticancer properties of CBG, CBC, CBN, and CBDV on MM cells, examining their effects on cell viability, invasion towards bone cells, and bone resorption. The study also investigated the efficacy of CBN in an in vivo MM xenograft mouse model.
- Inhibition of MM Cell Growth:
The researchers evaluated the impact of CBG, CBC, CBN, and CBDV on the viability of three different MM cell lines (U266, RPMI, and SKO). All four cannabinoids significantly reduced cell viability in a dose-dependent manner, with CBN and CBDV being the most effective, followed by CBG and CBC. The half-maximal inhibitory concentration (IC50) values indicated that CBN and CBDV were particularly potent in inhibiting MM cell growth.
- Induction of Necrotic Cell Death:
To further understand how these cannabinoids inhibit MM cell growth, the study used flow cytometry to assess cell death. Treatment with the IC50 dose of each cannabinoid for 48 hours induced necrotic cell death, as indicated by an increased percentage of propidium iodide (PI) positive cells. Western blot analysis showed an increased expression of γ-H2AX, a marker of DNA damage, further confirming cannabinoid-induced necrotic cell death.
- Reduction of MM Cell Invasion and Bone Resorption:
MM cells infiltrate the bone marrow and disrupt bone homeostasis by promoting osteoclast activity, leading to bone destruction. The study tested the effect of CBG, CBC, CBN, and CBDV on the invasion of MM cells towards osteoblasts, the cells responsible for bone formation. All four cannabinoids significantly reduced MM cell invasion, with CBG and CBN being the most effective. Additionally, these cannabinoids reduced bone resorption, as demonstrated by decreased levels of C-terminal type I collagen fragments, a biomarker for bone degradation.
- In Vivo Efficacy of CBN in Reducing Tumor Mass:
Based on the promising in vitro results, CBN was selected for in vivo testing in a xenograft mouse model of MM. Mice injected with MM cells were treated with CBN or a control substance every three days for three weeks. The results showed a significant reduction in tumor mass in the CBN-treated group compared to the control group, with no significant changes in body weight or organ weight, indicating that CBN was effective and well-tolerated.
Conclusion
This study suggests that minor phytocannabinoids—CBG, CBC, CBN, and CBDV—have significant potential as anticancer agents in the treatment of multiple myeloma. They not only inhibit MM cell growth and induce necrotic cell death but also reduce the invasive potential of MM cells towards bone and decrease bone resorption. Among these cannabinoids, CBN showed particular promise in reducing tumor mass in an in vivo model, highlighting its potential for further development as a therapeutic agent for MM.
Given these findings, further research is warranted to better understand the mechanisms by which these phytocannabinoids exert their effects and to explore their potential benefits in clinical settings. The continued exploration of cannabinoids could open new avenues for treating MM and possibly other hematological malignancies, offering hope to patients with limited treatment options.
https://iubmb.onlinelibrary.wiley.com/doi/full/10.1002/biof.2078
“Anticancer effect of minor phytocannabinoids in preclinical models of multiple myeloma.” (C. Aguzzi, et al., Biofactors, 2024)
