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

Posted on October 20, 2024 by David

“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

Cannabidiol Alleviates Oral Mucositis by Inhibiting PI3K/Akt/NF-κB-Mediated Pyroptosis

Posted on July 6, 2024 by David

“Background: Cannabidiol (CBD), extracted from Cannabis sativa, has anticancer, anti-inflammation, and analgesic effects. Nevertheless, its therapeutic effect and the mechanism by which it alleviates oral mucositis (OM) remain unclear.

Aims: To explore the impact of CBD on OM in mice and on human oral keratinocyte (HOK) cells.

Study design: Expiremental study.

Methods: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, GeneCard, DisGeNET, and Gene Expression Omnibus databases were used to conduct therapeutic target gene screening for drugs against OM. Cytoscape software was used to build networks linking components, targets, and diseases. The STRING database facilitated analysis of intertarget action relationships, and the target genes were analyzed for Kyoto Encyclopedia of Genes and Genomes pathway enrichment. Occurrence of serum inflammation-related factors, hematoxylin and eosin staining, and immunohistochemistry were used to assess OM injury. Cell proliferation, migration, pyroptosis, and apoptosis of HOK cells under different treatments were assessed. Molecular mechanisms were elucidated through western blot and quantitative real-time polymerase chain reaction analyses.

Results: A total of 49 overlapping genes were pinpointed as potential targets, with NF-κB1, PIK3R1, NF-κBIA, and AKT1 being recognized as hub genes among them. Additionally, the PI3K/Akt/NF-κB and interleukin-17 signaling pathways were identified as relevant. Our in vivo experiments showed that CBD significantly reduced the proportion of lesion area, mitigated oral mucosal tissue lesions, and downregulated the expression levels of genes and levels of proteins, including NLRP3, P65, AKT, and PI3K. In vitro experiments indicated that CBD enhanced HOK cell proliferation and migration and reduced apoptosis through inhibition of the PI3K/Akt/NF-κB signaling pathway and pyroptosis.

Conclusion: Our findings suggest a novel mechanism for controlling OM, in which CBD suppresses the PI3K/Akt/NF-κB signaling pathway and pyroptosis, thereby mitigating OM symptoms.”

https://pubmed.ncbi.nlm.nih.gov/38966918/

“Our study used bioinformatics data analysis alongside experimental validation, providing novel insights into the therapeutic role of CBD in OM. We discovered that CBD can alleviate pyroptosis in OM through the PI3K/AKT/NF-κB pathway. “

http://balkanmedicaljournal.org/text.php?lang=en&id=2614

Role of Cannabinoids in Oral Cancer

Posted on January 23, 2024 by David

“Cannabinoids have incited scientific interest in different conditions, including malignancy, due to increased exposure to cannabis. Furthermore, cannabinoids are increasingly used to alleviate cancer-related symptoms. This review paper aims to clarify the recent findings on the relationship between cannabinoids and oral cancer, focusing on the molecular mechanisms that could link cannabinoids with oral cancer pathogenesis. In addition, we provide an overview of the current and future perspectives on the management of oral cancer patients using cannabinoid compounds.

Epidemiological data on cannabis use and oral cancer development are conflicting. However, in vitro studies assessing the effects of cannabinoids on oral cancer cells have unveiled promising anti-cancer features, including apoptosis and inhibition of cell proliferation. Downregulation of various signaling pathways with anti-cancer effects has been identified in experimental models of oral cancer cells exposed to cannabinoids. Furthermore, in some countries, several synthetic or phytocannabinoids have been approved as medical adjuvants for the management of cancer patients undergoing chemoradiotherapy.

Cannabinoids may improve overall well-being by relieving anxiety, depression, pain, and nausea. In conclusion, the link between cannabinoid compounds and oral cancer is complex, and further research is necessary to elucidate the potential risks or their protective impact on oral cancer.”

https://pubmed.ncbi.nlm.nih.gov/38256042/

https://www.mdpi.com/1422-0067/25/2/969

Therapeutic targeting of the tumor microenvironments with cannabinoids and their analogs: Update on clinical trials

Posted on May 7, 2023 by David

“Cancer is a major global public health concern that affects both industrialized and developing nations. Current cancer chemotherapeutic options are limited by side effects, but plant-derived alternatives and their derivatives offer the possibilities of enhanced treatment response and reduced side effects.

A plethora of recently published articles have focused on treatments based on cannabinoids and cannabinoid analogs and reported that they positively affect healthy cell growth and reverse cancer-related abnormalities by targeting aberrant tumor microenvironments (TMEs), lowering tumorigenesis, preventing metastasis, and/or boosting the effectiveness of chemotherapy and radiotherapy.

Furthermore, TME modulating systems are receiving much interest in the cancer immunotherapy field because it has been shown that TMEs have significant impacts on tumor progression, angiogenesis, invasion, migration, epithelial to mesenchymal transition, metastasis and development of drug resistance.

Here, we have reviewed the effective role of cannabinoids, their analogs and cannabinoid nano formulations on the cellular components of TME (endothelial cells, pericytes, fibroblast and immune cells) and how efficiently it retards the progression of carcinogenesis is discussed. The article summarizes the existing research on the molecular mechanisms of cannabinoids regulation of the TME and finally highlights the human studies on cannabinoids’ active interventional clinical trials.

The conclusion outlines the need for future research involving clinical trials of cannabinoids to demonstrate their efficacy and activity as a treatment/prevention for various types of human malignancies.”

https://pubmed.ncbi.nlm.nih.gov/37146933/

https://www.sciencedirect.com/science/article/abs/pii/S0013935123006540?via%3Dihub

Real-Time Monitoring of the Cytotoxic and Antimetastatic Properties of Cannabidiol in Human Oral Squamous Cell Carcinoma Cells Using Electric Cell-Substrate Impedance Sensing

Posted on December 24, 2022 by David

“Cannabidiol (CBD) is an active natural compound that is extracted from Cannabis sativa. Previous studies show that CBD is a nonpsychotropic compound with significant anticancer effects.

This study determines its cytotoxic effect on oral cancer cells and OEC-M1 cells and compares the outcomes with a chemotherapeutic drug, cisplatin. This study has investigated the effect of CBD on the viability, apoptosis, morphology, and migration of OEC-M1 cells. Electric cell-substrate impedance sensing (ECIS) is used to measure the change in cell impedance for cells that are treated with a series concentration of CBD for 24 h.

AlamarBlue and annexin V/7-AAD staining assays show that CBD has a cytotoxic effect on cell viability and induces cell apoptosis. ECIS analysis shows that CBD decreases the overall resistance and morphological parameters at 4 kHz in a concentration-dependent manner. There is a significant reduction in the wound-healing recovery rate for cells that are treated with 30 μM CBD.

This study demonstrates that ECIS can be used for in vitro screening of new chemotherapy and is more sensitive, functional, and comprehensive than traditional biochemical assays. CBD also increases cytotoxicity on cell survival and the migration of oral cancer cells, so it may be a therapeutic drug for oral cancer.”

https://pubmed.ncbi.nlm.nih.gov/36555480/

“In conclusion, this study determines the effect of CBD on OEC-M1 cells. The cytotoxicity results show that CBD at higher concentrations (100 μM) increases cytotoxicity and is more likely to lead to the apoptosis of cancer cells more than cisplatin at the same concentration. ECIS is used to determine the effect of the drug on the adhesion, spread, and migration of cells.

The results show that there is a linear, concentration-dependent decrease in OEC-M1 cells that are treated with CBD. Treatment with CBD at low concentrations (30 μM) completely inhibits cell migration and micromotion without affecting cell viability and apoptosis.

In comparison with cisplatin, this study shows that CBD has a greater ability to inhibit metastasis and trigger apoptosis. It might work successfully as a treatment for oral cancer.

We can also screen drugs more efficiently and rapidly by using the Var32 analysis method in combination with ECIS. ECIS provides a more precise measurement of experimental data and prevents operator errors by its real-time monitoring. It is promising for possible uses in new drug screening, and it might promote the development of oral cancer treatments and other medical applications.”

https://www.mdpi.com/1422-0067/23/24/15842

Oxidative Stress and Autophagy Mediate Anti-Cancer Properties of Cannabis Derivatives in Human Oral Cancer Cells

Posted on October 14, 2022 by David

“Cannabinoids, the active components of cannabis exert palliative effects in cancer patients by preventing nausea, vomiting and pain as well as by stimulating appetite.

Recent studies indicated that cannabinoids could be helpful in treating certain rare forms of cancer and other inflammatory diseases.

The objective of this study was to investigate the cytotoxic effect of a cannabinoid mixture (CM) in oral cells. Thus, normal and cancer gingival cells were treated with different concentrations of CM to evaluate their proliferation by MTT assay, cytotoxicity by using LDH assay, colony formation with crystal violet and migration by the scratch method. In addition, apoptosis, autophagy, oxidative stress, antioxidant level, DNA damage and the mitochondrial membrane potential (ΔΨm) generated by proton pumps were measured by flow cytometry. Furthermore, deactivation of the key signaling pathways involved in cancer progression such as NF-κB, ERK1/2, p38, STAT1, STAT3, STAT5 was also evaluated by this technique.

These outcomes indicate that CM, at a concentration higher than 0.1 µg/mL, provokes high cytotoxicity in Ca9-22 oral cancer cells but not in GMSM-K gingival normal cells. Apoptosis, autophagy, antioxidant levels and mitochondrial stress as well as DNA damage in oral cells were increased following exposure to low concentration (1 µg/mL). In addition, major signaling pathways that are involved such as MAPKase, STATs and NF-κB pathways were inhibited by CM as well as cell migration.

Our results suggest that cannabinoids could potentially have a beneficial effect on oral cancer therapy.”

https://pubmed.ncbi.nlm.nih.gov/36230847/

“The therapeutic efficacy of cannabis is very limited and still needs to be confirmed or refuted. However, our recent work has shown that at low doses, cannabinoids (Δ9-THC and Δ8-THC), which are the main constituents of cannabis, are beneficial against oral cancer. In this current study, we showed that a mixture of cannabinoids (CM) can induce oral toxicity in cells by damaging the DNA and activating the mechanisms of autophagy and apoptosis along with inhibiting many cancer progression pathways such as MAPKase, STATs and NF-κB pathways. These data demonstrated clearly the potential beneficial effect of CM at low concentrations for oral cancer therapy.”

https://www.mdpi.com/2072-6694/14/19/4924/htm

Protective Effects of Cannabidiol on Chemotherapy-Induced Oral Mucositis via the Nrf2/Keap1/ARE Signaling Pathways

Posted on June 7, 2022 by David

“Oral mucositis (OM) is a common complication during chemotherapy characterized by ulceration, mucosa atrophy, and necrosis, which seriously interferes with nutritional intake and oncotherapy procedures among patients. However, the efficacy of current treatments for OM remains limited.

Cannabidiol (CBD) is a natural cannabinoid with multiple biological activities, including antioxidant and anti-inflammatory potential. In this study, we aimed to investigate the chemopreventive effects and mechanisms of CBD in protecting C57BL/6N mice and human oral keratinocytes (HOK) from 5-fluorouracil- (5-FU-) induced OM.

Here, we found that CBD alleviated the severity of 5-FU-induced OM in mice, including improved survival, decreased body weight loss, reduced ulcer sizes, and improved clinical scores. Histologically, CBD restored epithelial thickness and normal structure in tongue tissues. Meanwhile, CBD attenuated reactive oxygen species (ROS) overproduction and improved the antioxidant response, suppressed the inflammatory response, promoted the proliferation of epithelial cells, and inhibited 5-FU-induced apoptosis. In vitro, consistent outcomes showed that CBD suppressed cellular ROS levels, enhanced antioxidant ability, reduced inflammatory response, promoted proliferation, and inhibited apoptosis in 5-FU-treated HOK cells. In particular, CBD upregulated the expression levels of antioxidant enzymes, heme oxygenase-1 (HO-1) and NAD(P)H quinine oxidoreductase 1 (NQO1), by increasing the expression and nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and decreasing Kelch-like ECH-associated protein 1 (Keap1). Notably, the Nrf2 inhibitor ML385 reversed the protective effect of CBD. Nrf2-siRNA transfection also significantly blunted the antioxidant effect of CBD in in vitro OM model.

Collectively, our findings suggested that CBD protected against 5-FU-induced OM injury at least partially via the Nrf2/Keap1/ARE signaling pathways, highlighting the therapeutic prospects of CBD as a novel strategy for chemotherapy-induced OM.”

https://pubmed.ncbi.nlm.nih.gov/35669853/

“CBD alleviates chemotherapy-induced OM and protects against the toxicity of 5-FU by improving oxidative stress defense, downregulating mucosal inflammation, promoting cell proliferation, and inhibiting 5-FU-induced apoptosis both in mice and in HOK. Moreover, CBD-activated Nrf2/Keap1/ARE signaling pathways might be the underlying mechanism for OM recovery.”

https://www.hindawi.com/journals/omcl/2022/4619760/

The Effectiveness and Safety of Medical Cannabis for Treating Cancer Related Symptoms in Oncology Patients

Posted on May 30, 2022 by David

Frontiers in Pain Research (@FrontPain) / Twitter

“The use of medical cannabis (MC) to treat cancer-related symptoms is rising. However, there is a lack of long-term trials to assess the benefits and safety of MC treatment in this population. In this work, we followed up prospectively and longitudinally on the effectiveness and safety of MC treatment.

Oncology patients reported on multiple symptoms before and after MC treatment initiation at one-, three-, and 6-month follow-ups. Oncologists reported on the patients’ disease characteristics. Intention-to-treat models were used to assess changes in outcomes from baseline. MC treatment was initiated by 324 patients and 212, 158 and 126 reported at follow-ups.

Most outcome measures improved significantly during MC treatment for most patients (p < 0.005). Specifically, at 6 months, total cancer symptoms burden declined from baseline by a median of 18%, from 122 (82–157) at baseline to 89 (45–138) at endpoint (−18.98; 95%CI= −26.95 to −11.00; p < 0.001). Reported adverse effects were common but mostly non-serious and remained stable during MC treatment.

The results of this study suggest that MC treatment is generally safe for oncology patients and can potentially reduce the burden of associated symptoms with no serious MC-related adverse effects.

The main finding of the current study is that most cancer comorbid symptoms improved significantly during 6 months of MC treatment.

Additionally, we found that MC treatment in cancer patients was well tolerated and safe.”

https://pubmed.ncbi.nlm.nih.gov/35669038/

https://www.frontiersin.org/articles/10.3389/fpain.2022.861037/full?utm_source=fweb

“Cancer Pain Treatment Using Marijuana Safe and Effective, Large Study Finds”

https://www.newsweek.com/cannabis-medicinal-cancer-patient-symptoms-pain-relief-1711981

The Endocannabinoid System as a Pharmacological Target for New Cancer Therapies

Posted on April 13, 2022 by David

“Despite the long history of cannabinoid use for medicinal and ritual purposes, an endogenous system of cannabinoid-controlled receptors, as well as their ligands and the enzymes that synthesise and degrade them, was only discovered in the 1990s. Since then, the endocannabinoid system has attracted widespread scientific interest regarding new pharmacological targets in cancer treatment among other reasons.

Meanwhile, extensive preclinical studies have shown that cannabinoids have an inhibitory effect on tumour cell proliferation, tumour invasion, metastasis, angiogenesis, chemoresistance and epithelial-mesenchymal transition (EMT) and induce tumour cell apoptosis and autophagy as well as immune response. Appropriate cannabinoid compounds could moreover be useful for cancer patients as potential combination partners with other chemotherapeutic agents to increase their efficacy while reducing unwanted side effects.

In addition to the direct activation of cannabinoid receptors through the exogenous application of corresponding agonists, another strategy is to activate these receptors by increasing the endocannabinoid levels at the corresponding pathological hotspots. Indeed, a number of studies accordingly showed an inhibitory effect of blockers of the endocannabinoid-degrading enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) on tumour development and spread.

This review summarises the relevant preclinical studies with FAAH and MAGL inhibitors compared to studies with cannabinoids and provides an overview of the regulation of the endocannabinoid system in cancer.”

https://pubmed.ncbi.nlm.nih.gov/34830856/

“Cannabinoids have been shown to suppress tumour cell proliferation, tumour invasion, metastasis, angiogenesis, chemoresistance and epithelial-mesenchymal transition and to induce tumour cell apoptosis, autophagy and immune response. This review focuses on the current status of investigations on the impact of inhibitors of endocannabinoid-degrading enzymes on tumour growth and spread in preclinical oncology research.”

https://www.mdpi.com/2072-6694/13/22/5701

Plant-derived cannabinoids as anticancer agents

Posted on March 30, 2022 by David

“Substantial preclinical evidence demonstrates the antiproliferative, cytotoxic, and antimetastatic properties of plant-derived cannabinoids (phytocannabinoids) such as cannabidiol and tetrahydrocannabinol. The cumulative body of research into the intracellular mechanisms and phenotypic effects of these compounds supports a logical, judicious progression to large-scale phase II/III clinical trials in certain cancer types to truly assess the efficacy of phytocannabinoids as anticancer agents.”

https://pubmed.ncbi.nlm.nih.gov/35260379/

www.thctotalhealthcare.com

Category Archives: Oral Cancer