Category Archives: Cancer

Cannabidiol Ameliorates Doxorubicin-Induced Myocardial Injury via Activating Hippo Pathway

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“Background: Doxorubicin (DOX) is a chemotherapeutic agent widely used for cancer treatment and has non-negligible cardiotoxicity. Some previous studies have reported that cannabidiol (CBD) has cardioprotective effects. In this study, we evaluated the protective effects of CBD against DOX-induced cardiomyocyte injury, and explored the downstream molecular mechanism.

Methods and materials: GSE193861, containing healthy myocardial tissues and myocardial tissues with DOX-induced injury, was analyzed to screen for the involved proteins and pathways. Molecular docking was performed to identify candidate drugs. After H9c2 cells were treated with DOX and CBD, their viability, oxidative stress, and apoptosis were assessed. After YAP depletion, the role of the Hippo pathway in CBD function was investigated. C57BL/6 mice were treated with DOX to establish an in vivo model, and CBD and verteporfin (VP) were used to treat the mice. Histological analyses and immunofluorescence were used to evaluate myocardial tissue injury, and apoptosis and oxidative stress of the myocardial tissues were also analyzed. Western blotting was used to investigate the regulatory effects of CBD on the Hippo and apoptosis-related pathways.

Results: Bioinformatic analysis suggested that the Hippo pathway was a crucial pathway involved in DOX-induced myocardial injury. Molecular docking showed that CBD targeted multiple regulators of the Hippo pathway. CBD showed cardioprotective effects against DOX-induced myocardial injury both in vitro and in vivo and regulated Hippo pathway activity in cardiomyocytes. After inactivation of the Hippo pathway by YAP knockdown or VP intervention, the protective effects of CBD were reversed.

Conclusion: For the first time, we revealed that CBD is likely to reduce DOX-induced myocardial injury by regulating the Hippo signaling pathway.”

https://pubmed.ncbi.nlm.nih.gov/39876987/

“Overall, this study reports that CBD alleviates DOX-induced myocardial injury by regulating the Hippo pathway.”

https://www.dovepress.com/cannabidiol-ameliorates-doxorubicin-induced-myocardial-injury-via-acti-peer-reviewed-fulltext-article-DDDT

Exploring the Therapeutic Potential of Cannabidiol in U87MG Cells: Effects on Autophagy and NRF2 Pathway

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“Cannabinoids include both endogenous endocannabinoids and exogenous phytocannabinoids, such as cannabidiol (CBD), and have potential as therapeutic agents in cancer treatment due to their selective anticancer activities.

CBD exhibits both antioxidant and pro-oxidant effects depending on its concentration and cell types. These properties allow CBD to influence oxidative stress responses and potentially enhance the efficacy of antitumor therapies.

In this study, we treated U87MG glioma cells with low dose (1 μM) CBD and evaluated its molecular effects.

Our findings indicate that CBD reduced cell viability by 20% (p < 0.05) through the alteration of mitochondrial membrane potential. The alteration of redox status by CBD caused an attempt to rescue mitochondrial functionality through nuclear localization of the GABP transcription factor involved in mitochondria biogenesis. Moreover, CBD treatment caused an increase in autophagic flux, as supported by the increase in Beclin-1 and the ratio of LC3-II/LC3-I. Due to mitochondria functionality alteration, pro-apoptotic proteins were induced without activating apoptotic effectors Caspase-3 or Caspase-7. The study of the transcription factor NRF2 and the ubiquitin-binding protein p62 expression revealed an increase in their levels in CBD-treated cells.

In conclusion, low-dose CBD makes U87MG cells more vulnerable to cytotoxic effects, reducing cell viability and mitochondrial dynamics while increasing autophagic flux and redox systems. This explains the mechanisms by which glioma cells respond to CBD treatment.

These findings highlight the therapeutic potential of CBD, suggesting that modulating NRF2 and autophagy pathways could represent a promising strategy for glioblastoma treatment.”

https://pubmed.ncbi.nlm.nih.gov/39857352/

“Our study demonstrates that low-dose CBD treatment (1 μM) in U87MG glioblastoma cells stimulates the autophagy process, which is essential for mitochondrial renewal, contributing to an increase in mitochondria with altered membrane potential. Moreover, CBD-treated U87MG cells present an abnormal activation of the NRF2 pathway, reducing the expression of antioxidant target genes and consequently altering mitochondrial integrity. These molecular effects suggest that CBD could have therapeutic repercussions or be useful in the development of multi-target agents acting on the NRF2 mitochondrial biogenesis–autophagy axis.”

https://www.mdpi.com/2076-3921/14/1/18

Cannabidiol suppresses proliferation and induces cell death, autophagy and senescence in human cholangiocarcinoma cells via the PI3K/AKT/mTOR pathway

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“Background and aim: Cholangiocarcinoma (CCA) is usually diagnosed at a late stage, leading to treatment failure. Cannabidiol (CBD), exhibits diverse anti-cancer effects in various cancers, offering avenues for improving CCA treatment. This study investigated the effects of CBD on human CCA cells and the underlying mechanisms in vitro and in vivo.

Experimental procedure: The effects of CBD on three CCA cell lines (KKU-213B, KKU-100, KKU-055) were assessed using the SRB assay, clonogenic assay, cell cycle arrest, and 3D holotomography. Morphological changes were examined using transmission electron microscopy, while mitochondrial ROS levels and mitochondrial membrane potential were studied using MitoSOX, JC-1, and DCFH-DA. Cellular senescence induction was evaluated via SA-β-gal staining. Protein associatedwith autophagy and cellular senescence were analyzed using Western blot and/or immunofluorescent assays. A xenograft model demonstrated the anti-tumor activity of CBD and the induction of cellular senescence through immunohistochemistry targeting PCNA, β-gal, and p21.

Results and conclusion: CBD effectively inhibited CCA cell proliferation, suppressed colony formation and induced G0/G1 phase cell cycle arrest. Morphological examination revealed lipid droplets/vesicles in CCA cell lines. CBD induced autophagy by upregulating LC3BII, downregulating p62, and inhibiting the p-PI3K, p-AKT, and p-mTOR pathways. Additionally, CBD disrupted mitochondrial homeostasis by elevating ROS, reducing membrane potential, and induced cellular senescence by increasing the expression of p53 and p21. In-vitro results were confirmed by xenograft models. Overall, CBD suppresses proliferation and induces cell death, autophagy and senescence in CCA cells via the PI3K/AKT/mTOR pathway, which indicates a therapeutic option for CCA treatment.”

https://pubmed.ncbi.nlm.nih.gov/39850601/

“Although CBD has shown anti-tumor activity in various solid tumors, including CCA, its mechanism of action remains poorly understood.”

“The study reported here has shown that CBD has a significant anti-tumor effect on CCA cells through various mechanisms, including the inhibition of cell proliferation both in vitro and in vivo, the reduction of colony formation ability and the induction of multiple cellular processes, notably autophagy, cell cycle arrest, cellular senescence, mitochondrial dysfunction, lipid droplet formation, and ROS overproduction.

The significant findings from our study strongly suggest that CBD, through its targeting of the PI3K/AKT/mTOR pathway, holds great promise as a therapeutic agent for treating CCA and potentially other cancers.”

“Various herbal agents, including CBD, have shown promise for the treatment of CCA.”

https://www.sciencedirect.com/science/article/pii/S2225411024000506?via%3Dihub

Unveiling cellular changes in leukaemia cell lines after cannabidiol treatment through lipidomics

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“The present study was aimed at revealing the metabolic changes that occurred in the cellular lipid pattern of acute and chronic myeloid leukaemia cells following treatment with cannabidiol (CBD).

CBD is a non-psychoactive compound present in Cannabis sativa L., which has shown an antiproliferative action in these type of cancer cells.

CBD treatment reduced cell viability and initiated apoptotic and necrotic processes in both cancer cell lines in a time and dose-dependent manner, showing acute myeloid leukaemia (HL-60) cells greater sensitivity than chronic myeloid leukaemia ones (K-562), without differences in the activation of caspases 3/7. Then, control and treated cells of HL-60 and K-562 cell lines were studied through an untargeted lipidomic approach.

The treatment was carried out with CBD at a concentration of 10 μM for HL-60 cells and 23 µM CBD for K-562 cells for 48 h. After the extraction of the lipid content from cell lysates, the samples were analysed by UHPLC-QTOF-MS/MS both in the positive and the negative ionization modes. The comprehensive characterization of cellular lipids unveiled several classes significantly affected by CBD treatment. Most of the differences correspond to phospholipids, including cardiolipins (CL), phosphatidylcholines (PC) and phosphosphingolipids (SM), and also triacylglycerols (TG), being many TG species increased after CBD treatment in the acute and chronic models, whereas phospholipids were found to be decreased.

The results highlight some important lipid alterations related to CBD treatment, plausibly connected with different metabolic mechanisms involved in the process of cell death by apoptosis in cancer cell lines.”

https://pubmed.ncbi.nlm.nih.gov/39824876/

“Cannabinoids have shown to be effective both as a single agent and in combination with antineoplastic drugs.”

https://www.nature.com/articles/s41598-025-86044-5

Lebanese Cannabis sativa L. extract protects from cisplatin-induced nephrotoxicity in mice by inhibiting podocytes apoptosis

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“Background: Cisplatin is an anti-cancer drug used to treat a plethora of solid tumors. However, it is associated with dose dependent nephrotoxicity limiting its use as anticancer agent.

Objective: The current study aimed to investigate the nephroprotective effect of native Lebanese Cannabis sativa in both in vitro and in vivo mice model of cisplatin-induced nephrotoxicity.

Methods: Podocytes cell viability was assessed using MTS assay with cisplatin (30µM) in presence or absence of Cannabis oil extract (COE) at 0.5, 1 and 2µg/ml for 24h. Acute renal injury was established in adult female C57BL/6 mice with 20mg/kg, i.p. single dose cisplatin. Mice were divided into control group (vehicle), COE group, cisplatin group and cisplatin plus COE (2.5, 5 and 20mg/kg, i.p.). Animal body weight, serum creatinine, blood urea nitrogen (BUN), and proteinuria were measured.

Results: Cell viability assay and western blot analysis revealed that COE prevented apoptosis induced by cisplatin in cultured immortalized rat podocytes. In addition, in vitro scratch assay demonstrated the ability of COE to promote and restore the migratory capacity of podocytes in cisplatin-treated cells. Interestingly, COE treatment improved urinary and serum parameters characterized by a significant decrease in serum creatinine, urea, and proteinuria at various COE doses. Western blot analysis showed that COE inhibited COX-2 protein induction as well as apoptosis marker production (Bax/Bcl2 ratio) in cisplatin-treated mice when compared to mice treated with cisplatin alone.

Conclusion: Collectively, the aforementioned findings indicate that COE could be a promising approach to protect against cisplatin-induced nephrotoxicity.”

https://pubmed.ncbi.nlm.nih.gov/39819647/

“In conclusion, our results corroborated previous findings but on kidney podocytes. We strongly suggest that the Lebanese Cannabis oil extract may be of significant therapeutic benefits against the renal complications of cisplatin. Thus, Lebanese COE produces its renoprotective effects partly through activating antiinflammatory and antiapoptoric mechanisms in podocytes.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00260-4

The Role of Cannabinoids and the Endocannabinoid System in the Treatment and Regulation of Nausea and Vomiting

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“Despite using the recommended anti-emetic treatments, control of nausea and vomiting is still an unmet need for cancer patients undergoing chemotherapy treatment. Few properly controlled clinical trials have evaluated the potential of exogenously administered cannabinoids or manipulations of the endogenous cannabinoid (eCB) system to treat nausea and vomiting. In this chapter, we explore the pre-clinical and human clinical trial evidence for the potential of exogenous cannabinoids and manipulations of the eCB system to reduce nausea and vomiting. Although there are limited high-quality human clinical trials, pre-clinical evidence suggests that cannabinoids and manipulations of the eCB system have anti-nausea/anti-emetic potential. The pre-clinical anti-nausea/anti-emetic evidence highlights the need for further evaluation of cannabinoids and manipulations of eCBs and other fatty acid amides in clinical trials.”

https://pubmed.ncbi.nlm.nih.gov/39739175/

https://link.springer.com/chapter/10.1007/7854_2024_554

The Anticancer Activity of Cannabinol (CBN) and Cannabigerol (CBG) on Acute Myeloid Leukemia Cells

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“Several cannabis plant-derived compounds, especially cannabinoids, exhibit therapeutic potential in numerous diseases and conditions.

In particular, THC and CBD impart palliative, antiemetic, as well as anticancer effects.

The antitumor effects include inhibition of cancerous cell growth and metastasis and induction of cell death, all mediated by cannabinoid interaction with the endocannabinoid system (ECS). However, the exact molecular mechanisms are still poorly understood. In addition, their effects on leukemia have scarcely been investigated.

The current work aimed to assess the antileukemic effects of CBN and CBG on an acute monocytic leukemia cell line, the THP-1. THP-1 cell viability, morphology and cell cycle analyses were performed to determine potential cytotoxic, antiproliferative, and apoptotic effects of CBN and CBG. Western blotting was carried out to measure the expression of the proapoptotic p53.

Both CBN and CBG inhibited cell growth and induced THP-1 cell apoptosis and cell cycle arrest in a dose- and time-dependent manner. CBN and CBG illustrated different dosage effects on THP-1 cells in the MTT assay (CBN > 40 μΜ, CBG > 1 μM) and flow cytometry (CBN > 5 μM, CBG > 40 μM), highlighting the cannabinoids’ antileukemic activity.

Our study hints at a direct correlation between p53 expression and CBG or CBN doses exceeding 50 μM, suggesting potential activation of p53-associated signaling pathways underlying these effects.

Taken together, CBG and CBN exhibited suppressive, cell death-inducing effects on leukemia cells. However, further in-depth research will be needed to explore the molecular mechanisms driving the anticancer effects of CBN and CBG in the leukemia setting.”

https://pubmed.ncbi.nlm.nih.gov/39770061/

https://www.mdpi.com/1420-3049/29/24/5970

Tobacco and marijuana use and their association with serum prostate-specific antigen levels among African American men in Chicago

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“African American (AA) men experience more than twice the prostate cancer mortality as White men yet are under-represented in academic research involving prostate-specific antigen (PSA), a biomarker of prostate cancer aggressiveness.

We examined the impact of self-reported tobacco (cigarette pack-years and current tobacco use including e-cigarettes) and current regular marijuana use on serum PSA level based on clinical laboratory testing among 928 AA men interviewed 2013-2018 in Chicago. We defined outcome of elevated PSA ≥ 4.0 ng/mL for logistic regression models and continuous PSA increases for general linear models. All models were adjusted for age, sociodemographic characteristics, healthcare utilization, body mass index, and self-reported health.

Among 431 AA men age ≥ 55 years, we observed ∼ 5 times the odds of elevated PSA among those with > 1 pack-years of cigarette smoking vs. never-smokers (odds ratio [OR] = 5.09; 95% confidence interval [CI] = 1.57-16.6) and a quarter the odds of elevated PSA among current marijuana users vs. non-users (OR = 0.27; 95% CI = 0.08-0.96). PSA increased on average 1.20 ng/mL among other current tobacco users vs. non-users.

Among older AA men, cigarette smoking history and current tobacco use were positively associated with an increase in PSA levels and current marijuana use were inversely associated with PSA levels.

Future work with studies of diverse patient populations with cancer outcomes are needed to assess whether these behavioral characteristics contribute to racial/ ethnic disparities in prostate cancer outcomes.

Our study provides novel evidence regarding potential differences in PSA levels among older AA men according to behavioral characteristics.”

https://pubmed.ncbi.nlm.nih.gov/33088675/

“Tobacco use was associated with an increase in PSA among older AA men.”

“Marijuana use was associated with a decrease in PSA among older AA men.”

https://www.sciencedirect.com/science/article/pii/S2211335520301339


Cannabidiol Suppresses Metastatic Castration-Resistant Prostate Cancer Progression and Recurrence through Modulating Tryptophan Catabolism

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“Metastatic castration-resistant prostate cancer (mCRPC) is an aggressive phenotype of prostate cancer (PC). Tryptophan oxidative catabolism by indoleamine 2,3-dioxygenase-1 (IDO1) cleaves the indole ring to kynurenine (Kyn), an endogenous ligand for the aryl hydrocarbon receptor (AhR), which activates multiple tumorigenesis pathways. The IDO1-Kyn-AhR axis is aberrantly dysregulated in mCRPC. (-)-

Cannabidiol (CBD) is a nonpsychoactive phytocannabinoid. CBD showed antitumor activities against human malignancies, including PC.

CBD showed potent in vitro dose-dependent reduction of viability and clonogenicity of diverse human PC cell lines. CBD reduced the expression of IDO1 and AhR in PC cells. A daily 15 mg/kg oral dose of CBD for 30 days effectively suppressed the progression of the mCRPC CWR-R1ca-Luc cells xenografted in male nude mice. Continued CBD oral dosing for an additional 45 days suppressed the CWR-R1ca-Luc tumor locoregional and distant recurrences after the primary tumors’ surgical excision.

Collected CBD-treated tumors showed a reduced level of IDO1 expression. CBD-treated mice displayed a significant systemic reduction of Kyn.

CBD is a novel, nonpsychoactive phytocannabinoid lead useful for the control of mCRPC via targeting the tryptophan catabolism.”

https://pubmed.ncbi.nlm.nih.gov/39698265/

https://pubs.acs.org/doi/10.1021/acsptsci.4c00448

Cannabidiol promotes apoptosis and downregulation of oncogenic factors

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“Patients with high-grade serous carcinoma of tubo-ovarian origin (HGSC) often experience significant side effects related to their disease and treatments, such as pain, discomfort, nausea, and vomiting.

Over the last two decades, the use of cannabinoids (CBD) to manage pain and anxiety has become more mainstream. However, there is limited data on how CBD interacts with HGSC tumor cells or whether CBD impacts the effect of chemotherapy.

Prior preclinical data has suggested the antitumor benefits of cannabinoids; however, the mechanism and data in ovarian cancer are limited.

The objectives of this proposed research are to define the endocannabinoid system milieu in ovarian cancer, determine if CBD influences the growth of ovarian cancer cells, measure the cell viability when cannabinoids such as CBD are combined with standard-of-care therapies, and identify potential molecular pathways in which cannabinoids have a therapeutic effect.

We conducted publicly available database searches, in vitro proliferation and apoptotic assays, functional protein signaling via reverse phase protein array analysis of CBD-treated cells using 2D cultured cells, and immunohistological analysis of ex vivo cultured patient-derived tumor slices treated with CBD.

Our data suggests that CBD is unlikely to affect the growth of cancer cells at physiologic doses but promotes apoptosis and can have growth inhibitory effects at higher concentrations.

The inhibitory effects seen at high dose concentrations are likely from the upregulation of apoptotic pathways and inhibition of oncogenic pathways. Overall, physiologic CBD levels have minimal impact on cancer cell growth or chemotherapy efficacy.”

https://pubmed.ncbi.nlm.nih.gov/39677720/

https://www.biorxiv.org/content/10.1101/2024.11.30.626177v1