Category Archives: Cancer

The evolution of cannabinoid receptors in cancer

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“Cannabis sativa (cannabis) has been used as a therapeutic treatment for centuries treating various diseases and disorders. However, racial propaganda led to the criminalization of cannabis in the 1930s preventing opportunities to explore marijuana in therapeutic development. The increase in recreational use of cannabis further grew concern about abuse, and lead to further restrictions and distribution of cannabis in the 1970s when it was declared to be a Schedule I drug in the USA. In the late 1990s in some states, legislation assisted in legalizing the use of cannabis for medical purposes under physician supervision.

As it has been proven that cannabinoids and their receptors play an essential role in the regulation of the physiological and biological processes in our bodies. The endocannabinoid system (ECS) is the complex that regulates the cell-signaling system consisting of endogenous cannabinoids (endocannabinoids), cannabinoid receptors, and the enzymes responsible for the synthesis and degradation of the endocannabinoids. The ECS along with phytocannabinoids and synthetic cannabinoids serves to be a beneficial therapeutic target in treating diseases as they play roles in cell homeostasis, cell motility, inflammation, pain-sensation, mood, and memory.

Cannabinoids have been shown to inhibit proliferation, metastasis, and angiogenesis and even restore homeostasis in a variety of models of cancer in vitro and in vivo. Cannabis and its receptors have evolved into a therapeutic treatment for cancers.”

https://pubmed.ncbi.nlm.nih.gov/36750231/

https://wires.onlinelibrary.wiley.com/doi/10.1002/wsbm.1602

Inhalant cannabidiol impedes tumor growth through decreased tumor stemness and impaired angiogenic switch in NCI-H1437-induced human lung cancer model

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SpringerLink

“Lung cancer remains the most chronic form of cancer and the leading cause of cancer mortality in the world. Despite significant improvements in the treatment of lung cancer, the current therapeutic interventions are only partially effective, necessitating the continued search for better, novel alternative treatments. Angiogenesis and cancer stem cells play a central role in the initiation and propagation of cancers. Tumor angiogenesis is triggered by an angiogenic switch when pro-angiogenic factors exceed anti-angiogenic components. Although many anti-angiogenic agents are used in cancer treatment, there are therapeutic limitations with significant side effects.

In recent years, cannabinoids have been investigated extensively for their potential anti-neoplastic effects. Our previous findings showed that cannabidiol (CBD) could impede tumor growth in mouse models of melanoma and glioblastoma.

Importantly, CBD has been suggested to possess anti-angiogenic activity.

In this study, we tested, for the first time, inhalant CBD in the treatment of heterotopic lung cancer and whether such potential effects could reduce cancer stem cell numbers and inhibit tumor angiogenesis.

We implanted NCI H1437 human lung cancer cells in nude mice and treated the mice with inhalant CBD or placebo. The outcomes were measured by tumor size and imaging, as well as by immunohistochemistry and flow cytometric analysis for CD44, VEGF, and P-selectin.

Our findings showed that CBD decreased tumor growth rate and suppressed expression of CD44 and the angiogenic factors VEGF and P-selectin.

These results suggest, for the first time, that inhalant CBD can impede lung cancer growth by suppressing CD44 and angiogenesis.”

https://pubmed.ncbi.nlm.nih.gov/36737540/

https://link.springer.com/article/10.1007/s13577-023-00869-8

Cannabidiol alters mitochondrial bioenergetics via VDAC1 and triggers cell death in hormone-refractory prostate cancer

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Pharmacological Research

“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 signalling.

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 signalling 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://pubmed.ncbi.nlm.nih.gov/36736415/

https://www.sciencedirect.com/science/article/pii/S1043661823000397?via%3Dihub

Tetrahydrocannabinols: potential cannabimimetic agents for cancer therapy

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SpringerLink

“Tetrahydrocannabinols (THCs) antagonize the CB1 and CB2 cannabinoid receptors, whose signaling to the endocannabinoid system is essential for controlling cell survival and proliferation as well as psychoactive effects. Most tumor cells express a much higher level of CB1 and CB2; THCs have been investigated as potential cancer therapeutic due to their cannabimimetic properties. To date, THCs have been prescribed as palliative medicine to cancer patients but not as an anticancer modality.

Growing evidence of preclinical research demonstrates that THCs reduce tumor progression by stimulating apoptosis and autophagy and inhibiting two significant hallmarks of cancer pathogenesis: metastasis and angiogenesis.

However, the degree of their anticancer effects depends on the origin of the tumor site, the expression of cannabinoid receptors on tumor cells, and the dosages and types of THC. This review summarizes the current state of knowledge on the molecular processes that THCs target for their anticancer effects. It also emphasizes the substantial knowledge gaps that should be of concern in future studies. We also discuss the therapeutic effects of THCs and the problems that will need to be addressed in the future. Clarifying unanswered queries is a prerequisite to translating the THCs into an effective anticancer regime.”

https://pubmed.ncbi.nlm.nih.gov/36696005/

https://link.springer.com/article/10.1007/s10555-023-10078-2

The Effect of Cannabis Plant Extracts on Head and Neck Squamous Cell Carcinoma and the Quest for Cannabis-Based Personalized Therapy

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“Cannabis sativa plants have a wide diversity in their metabolite composition among their different chemovars, facilitating diverse anti-tumoral effects on cancer cells. This research examined the anti-tumoral effects of 24 cannabis extracts representative of three primary types of chemovars on head and neck squamous cell carcinoma (HNSCC). The chemical composition of the extracts was determined using High-Performance Liquid Chromatography (HPLC) and Mass Spectrometry (MS). The most potent anti-tumoral extracts were type III decarboxylated extracts, with high levels of Cannabidiol (CBD). We identified extract 296 (CAN296) as the most potent in inducing HNSCC cell death via proapoptotic and anti-proliferative effects. Using chemical fractionation of CAN296, we identified the CBD fraction as the primary inducer of the anti-tumoral activity. We succeeded in defining the combination of CBD with cannabichromene (CBC) or tetrahydrocannabinol (THC) present in minute concentrations in the extract, yielding a synergic impact that mimics the extract’s full effect. The cytotoxic effect could be maximized by combining CBD with either CBC or THC in a ratio of 2:1. This research suggests using decarboxylated CBD-type extracts enriched with CBC for future preclinical trials aimed at HNSCC treatment.”

https://pubmed.ncbi.nlm.nih.gov/36672446/

“The survival rate of head and neck cancer has only improved slightly over the last quarter century, raising the need for novel therapies to better treat this disease. This research examined the anti-tumor effects of 24 different types of cannabis extracts on head and neck cancer cells. Type III decarboxylated extracts with high levels of Cannabidiol (CBD) were the most effective in killing cancer cells. From these extracts, the specific active molecules were recognized. Combining CBD with Cannabichromene (CBC) in a 2:1 ratio made the effect even stronger. These findings can help doctors match cannabis extracts to treat head and neck cancer. CBD extracts enriched with the non-psychoactive CBC can offer patients more effective treatment. Further research is needed to develop new topical treatments from such extracts.”

“This research suggests using whole cannabis extracts, which are decarboxylated CBD-rich, to induce cancer cell death. In recent years many cancer patients have been treated with cannabis extracts as a palliative treatment. Based on this research, these chemovars can provide additional anti-cancer properties in addition to the palliative effects that cancer patients can benefit from.”

https://www.mdpi.com/2072-6694/15/2/497

Therapeutic and Supportive Effects of Cannabinoids in Patients with Brain Tumors (CBD Oil and Cannabis)

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SpringerLink

“The potential medicinal properties of Cannabis continue to garner attention, especially in the brain tumor domain. This attention is centered on quality of life and symptom management; however, it is amplified by a significant lack of therapeutic choices for this specific patient population.

While the literature on this matter is young, published and anecdotal evidence imply that cannabis could be useful in treating chemotherapy-induced nausea and vomiting, stimulating appetite, reducing pain, and managing seizures. It may also decrease inflammation and cancer cell proliferation and survival, resulting in a benefit in overall patient survival.

Current literature poses the challenge that it does not provide standardized guidance on dosing for the above potential indications and cannabis use is dominated by recreational purposes. Furthermore, integrated and longitudinal studies are needed but these are a challenge due to arcane laws surrounding the legality of such substances. The increasing need for evidence-based arguments about potential harms and benefits of cannabis, not only in cancer patients but for other medical use and recreational purposes, is desperately needed.”

https://pubmed.ncbi.nlm.nih.gov/36633803/

https://link.springer.com/article/10.1007/s11864-022-01047-y

Phytochemical Constituents and Derivatives of Cannabis sativa; Bridging the Gap in Melanoma Treatment

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“Melanoma is deadly, physically impairing, and has ongoing treatment deficiencies. Current treatment regimens include surgery, targeted kinase inhibitors, immunotherapy, and combined approaches. Each of these treatments face pitfalls, with diminutive five-year survival in patients with advanced metastatic invasion of lymph and secondary organ tissues. Polyphenolic compounds, including cannabinoids, terpenoids, and flavonoids; both natural and synthetic, have emerging evidence of nutraceutical, cosmetic and pharmacological potential, including specific anti-cancer, anti-inflammatory, and palliative utility. Cannabis sativa is a wellspring of medicinal compounds whose direct and adjunctive application may offer considerable relief for melanoma suffers worldwide. This review aims to address the diverse applications of C. sativa‘s biocompounds in the scope of melanoma and suggest it as a strong candidate for ongoing pharmacological evaluation.”

https://pubmed.ncbi.nlm.nih.gov/36614303/

“In conclusion, there is a complex array of effects that polyphenolic and cannabinoid compounds elicit in relation to melanoma. Multiple biochemical and genetic cascades are regulated through the presence of these natural substances. Polyphenolic compounds emergingly demonstrate a significant capacity to mediate many of the impacts of cancer, including pain, inflammation and invasiveness. Combined administration of polyphenol compounds has shown existing promise for improvement of potency and bioactivity of these substances. To combat the complexity of cancer, new pharmacological perspectives are necessary. Accordingly, plant polyphenols, particularly those of cannabis provide a deep well of structural potential for the emergence of novel drugs with multi-applicability to the total sphere of cancer treatment. This is merely the budding tip of biocompounds available for exploration in plant-based medicine and is a substantive base for future research.”

https://www.mdpi.com/1422-0067/24/1/859

Cannabidiol as Self-Assembly Inducer for Anticancer Drug-Based Nanoparticles

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“Cannabidiol (CBD) is a biologically active compound present in the plants of the Cannabis family, used as anticonvulsant, anti-inflammatory, anti-anxiety, and more recently, anticancer drug. In this work, its use as a new self-assembly inducer in the formation of nanoparticles is validated. The target conjugates are characterized by the presence of different anticancer drugs (namely N-desacetyl thiocolchicine, podophyllotoxin, and paclitaxel) connected to CBD through a linker able to improve drug release. These nanoparticles are formed via solvent displacement method, resulting in monodisperse and stable structures having hydrodynamic diameters ranging from 160 to 400 nm. Their biological activity is evaluated on three human tumor cell lines (MSTO-211H, HT-29, and HepG2), obtaining GI50 values in the low micromolar range. Further biological assays were carried out on MSTO-211H cells for the most effective NP 8B, confirming the involvement of paclitaxel in cytotoxicity and cell death mechanism.”

https://pubmed.ncbi.nlm.nih.gov/36615306/

https://www.mdpi.com/1420-3049/28/1/112

Formulation and development of novel lipid-based combinatorial advanced nanoformulation for effective treatment of non-melanoma skin cancer

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International Journal of Pharmaceutics

“Non-melanoma skin cancer is one of the most common malignancies reported with high number of morbidities, demanding an advanced treatment option with superior chemotherapeutic effects. Due to high degree of drug resistance, conventional therapy fails to meet the desired therapeutic efficacy. To break the bottleneck, nanoparticles have been used as next generation vehicles that facilitate the efficient interaction with the cancer cells.

Here, we developed combined therapy of 5-fluorouracil (5-FU) and cannabidiol (CBD)-loaded nanostructured lipid carrier gel (FU-CBD-NLCs gel). The NLCs were optimized using central composite design that showed an average particle size of 206 nm and a zeta potential of -34 mV. In addition, in vitro and ex vivo drug permeations studies demonstrated the effective delivery of both drugs in the skin layers via lipid structured nanocarriers.

Also, the prepared FU-CBD-NLCs showed promising effect in-vitro cell studies including MTT assays, wound healing and cell cycle as compared to the conventional formulation. Moreover, dermatokinetic studies shows there was superior deposition of drugs at epidermal and the dermal layer when treated with FU-CBD-NLCs.

In the end, overall study offered a novel combinatorial chemotherapy that could be an option for the treatment of non-melanoma skin cancer.”

https://pubmed.ncbi.nlm.nih.gov/36608807/

https://www.sciencedirect.com/science/article/abs/pii/S0378517322011358?via%3Dihub

[A mini-review on anti-tumor effect of cannabidiol]

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“Cannabidiol is the main non-psychoactive component of Cannabis sativa, which has multiple medicinal activities, such as antiepileptic, immunomodulation, analgesic, antioxidant, anticonvulsant, anti-anxiety and other functions.

In recent years, it has been found that cannabidiol can inhibit the proliferation of various tumor cells, induce apoptosis and autophagy of tumor cells, arrest cell cycle, interrupt invasion and metastasis of tumor cells, regulate tumor microenvironment, exert synergistic therapy with other chemotherapeutic drugs, and reduce the toxicity of chemotherapeutic drugs. However, its anti-tumor effect remains controversial and its application is limited. The study of microspheres, nano liposomes and other new drug delivery systems can improve the anti-tumor effect of cannabidiol.

In this study, the anti-tumor mechanism and application of cannabidiol were summarized and discussed in order to provide inspirations for its further investigation and application.”

https://pubmed.ncbi.nlm.nih.gov/36604902/

https://kns.cnki.net/kcms/detail/detail.aspx?doi=10.19540/j.cnki.cjcmm.20220906.601