Category Archives: Cancer

Parthanatos and apoptosis: unraveling their roles in cancer cell death and therapy resistance

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“Cell death is a fundamental process that needs to be maintained to balance cellular functions and prevent disease. There are several cell death pathways; however, apoptosis and parthanatos are the most prominent and have important roles in cancer biology. As an extremely well-regulated process, apoptosis removes damaged or abnormal cells via caspase activation and mitochondrial involvement.

Unlike in the healthy cells, the loss of ability to induce apoptosis in cancer permits tumor cells to survive and multiply out of control and contribute to tumor progression and therapy resistance. On the contrary, parthanatos is a caspase-independent metabolic collapse driven by poly (ADP-ribose) polymerase 1 (PARP1) overactivation, translocation of apoptosis-inducing factor (AIF), and complete DNA damage. Several cancer models are involved with parthanatos. Deoxypodophyllotoxin (DPT) induces parthanatos in glioma cells by excessive ROS generation, PARP1 upregulation, and AIF nuclear translocation.

Like in acute myeloid leukemia (AML), the cannabinoid derivative WIN-55 triggers parthanatos, and the effects can be reversed by PARP inhibitors such as olaparib.

Developing cancer treatment strategies involving advanced cancer treatment strategies relies on the interplay between apoptosis and parthanatos. However, such apoptosis-based cancer therapies tend to develop resistance, so there is an urgent need to look into alternative pathways like parthanatos, which may not always trigger apoptosis.

In overcoming apoptosis resistance, there is evidence that combining apoptosis-inducing agents, such as BH3 mimetics, with PARP inhibitors synergistically enhances cell death.

Oxidative stress modulators have been found to promote the execution of parthanatic and apoptotic pathways and allow treatment. In this review, apoptosis and parthanatos are thoroughly compared at the molecular level, and their roles in cancer pathogenesis as related to cancer therapeutic potential are discussed.

We incorporate recent findings to demonstrate that not only can parthanatos be used to manage therapy resistance and enhance cancer treatment via the combination of parthanatos and apoptosis but also that immunity and bone deposition can feasibly be employed against long-circulating cancer stem cells to treat diverse forms of metastatic cancers.”

https://pubmed.ncbi.nlm.nih.gov/40166425/

“Cannabinoids induce cell death in leukaemic cells through Parthanatos and PARP-related metabolic disruptions.”

https://pubmed.ncbi.nlm.nih.gov/38461169/

Early oral administration of THC:CBD formulations prevent pain-related behaviors without exacerbating paclitaxel-induced changes in weight, locomotion, and anxiety in a rat model of chemotherapy-induced neuropathy

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“Rationale: Paclitaxel-induced neuropathy stands out as the primary, dose-limiting side effect of this extensively used chemotherapy agent. Prolonged hypersensitivity and pain represent the most severe clinical manifestations. Effective preventive and therapeutic strategies are currently lacking.

Objectives: Our study aimed to assess the impact of early oral administration of pharmaceutical-grade formulations containing the phytocannabinoids THC and CBD in a rat model of paclitaxel-induced neuropathy.

Methods: The experimental design involved the co-administration of paclitaxel and cannabinoid formulations with different THC to CBD ratios (THC:CBD 1:1 and THC:CBD 1:20) to adult male rats. Mechanical and thermal sensitivity, locomotor activity, vertical exploratory behaviors, anxiety-related parameters, weight gain, food and water consumption, and liver functionality were assessed.

Results: Daily administration of THC:CBD 1:1 successfully prevented paclitaxel-induced cold allodynia, while THC:CBD 1:20 effectively prevented both thermal and mechanical hypersensitivities. Additionally, THC:CBD 1:1 formulation restored rearing behavior, significantly reduced by paclitaxel. Conversely, neither cannabinoid formulation was able to counteract paclitaxel-induced hypo-locomotion, reduced vertical exploratory activity, increased anxiety-like behaviors, attenuated weight gain, or decreased food and water intakes. However, the formulations employed did not induce further alterations or toxicity in animals receiving paclitaxel, and no signs of liver damage were detected.

Conclusions: Our results suggest a differential therapeutic effect of two THC:CBD formulations on pain-related behaviors and spontaneous activities, particularly in the context of peripheral neuropathy. These formulations represent a promising therapeutic strategy not only to managing pain but also for enhancing daily activities and improving the quality of life for cancer patients.”

https://pubmed.ncbi.nlm.nih.gov/40163146/

Extraction of Cannabinoids and Terpenes from Hemp Flowers and Leaves (Cannabis sativa L., Futura 75): Chemical Profiling and Evaluation of Anticancer Properties

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“This study investigated efficient extraction methods for cannabinoids and terpenes from the above-ground parts of Futura 75, focusing on two techniques: pressurized extraction and magnetic stirrer-assisted extraction. The effects of solvent type, temperature, time, and pressure were evaluated using five organic solvents and two binary solvent systems.

Cannabinoid profiles of obtained extracts were analyzed using gas chromatography coupled with mass spectrometry (GC-MS), while terpene profiles were characterized through solid-phase microextraction (SPME) combined with GC-MS. Next, two selected extracts with the highest content of cannabinoid and terpene fractions (Futu1 and Futu2) were tested for antiproliferative activity toward cancer cell lines (MV4-11, AGS, HT-29, MDA-MB-468, MCF-7) and their cytotoxicity was evaluated on non-tumorigenic MCF-10A cells. Extract Futu1 contained 51.57% cannabinoids, 9.8% monoterpenes, and 90.2% sesquiterpenes in the terpene fraction. Futu2 exhibited a higher proportion of monoterpenes in the terpene fraction (19.6% monoterpenes and 80.4% sesquiterpenes) and consisted of 49.49% cannabinoids.

Both extracts exhibited higher selectivity for cancer cells over non-tumorigenic cells, with Futu2 demonstrating stronger antiproliferative properties.”

https://pubmed.ncbi.nlm.nih.gov/40142100/

“Cannabis sativa L., commonly known as hemp, belongs to the Cannabaceae family, which includes two primary cannabis varieties: hemp (Cannabis sativa L. var. sativa) and marijuana (Cannabis sativa L. var. indica).”

“The effects of two selected extracts from the Futura 75 hemp variety—containing cannabinoids and terpene fractions with differing monoterpene-to-sesquiterpene ratios—were investigated for their potential to inhibit cancer cell growth and their safety concerning healthy breast cells. The results indicate that while the extracts are less active than the tested individual cannabinoids, they exhibit significantly higher selectivity toward cancer cells compared to non-tumorigenic cells. Furthermore, the extract with a higher monoterpene content (Futu 2) demonstrated slightly stronger antiproliferative activity.”

https://www.mdpi.com/1420-3049/30/6/1325

A Multicenter Feasibility Study of a Novel Curriculum for Oncology Trainees Regarding Medical Cannabis

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“Background: Oncology providers often lack the confidence to make clinical recommendations about medical cannabis (MC). This study aimed to develop and evaluate the feasibility of implementing an educational curriculum on the use of MC in patient care for oncology trainees.

Methods: A multidisciplinary team designed an educational curriculum for MC use in oncology. The curriculum was piloted as a 1-hour interactive webinar across 8 United States-based hematology/oncology fellowship programs between 2022 and 2023. Incentivized surveys measuring feasibility outcomes, including cultural attitudes/norms, acceptability, compatibility, and self-efficacy (a composite index of self-confidence in discussing MC efficacy, risks, modes of use, and role in symptom management), were distributed before, immediately after, and 12 weeks post-webinar.

Results: Of 103 trainees, 75 (72.8%) completed the pretraining survey and 66 (64.1%) completed the posttraining survey. Most respondents believed discussions about the role of MC in symptom management were valuable (n=56; 74.7%), though few (14.7%) believed trainees were expected to engage in such discussions. Most participants rated the curriculum as helpful (92.4%), beneficial for oncology trainees (84.8%), and likely to be recommended to colleagues (87.9%). Post-webinar, 78.8% of participants reported an increased likelihood of initiating discussions with patients regarding MC. There were significant improvements in the composite self-confidence index from pre- to post-webinar (2.7% vs 65.2%; P<.001), which persisted in the follow-up surveys (n=36; response rate, 34.9%).

Conclusions: This multisite study demonstrates the feasibility of implementing a novel curriculum focused on MC for oncology trainees. These findings can guide the design of a prospective, multi-institutional study to evaluate knowledge expansion, retention, and behavioral changes resulting from the intervention.”

https://pubmed.ncbi.nlm.nih.gov/40073833/

“Our prior work demonstrated that training in MC use for patients with cancer is an area of unmet need among hematology/oncology trainees. The current study demonstrated the feasibility and acceptability of developing and delivering a virtual webinar curriculum on MC for hematology/oncology fellows. Most trainees enjoyed the format and found the content useful and applicable to their practice and education. We observed sustained improvements in self-reported confidence in conducting clinical discussions across all domains included in the curriculum. Furthermore, participants reported increased discussions about MC with patients following the training, aligning with recent expert consensus guidelines. Future efforts should focus on refining this curriculum based on emerging data in the field, developing similar interventions for other oncology health care professionals, and exploring strategies to sustain these educational initiatives. Such efforts are essential to ensure broad implementation, maximize knowledge retention, and facilitate meaningful behavioral changes in real-world clinical practice.”

https://jnccn.org/view/journals/jnccn/23/3/article-p82.xml

A Green Microwave-Assisted Extraction of Cannabis sativa L. Extract and Its Cytotoxic Activity Against Cancer Cells

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“Objectives: This study aimed to explore the use of D-limonene and some vegetable oils with different amounts of saturated and unsaturated fatty acids as alternative green solvents for microwave-assisted extraction (MAE) of cannabis (Cannabis sativa L.). A standardized cannabis extract was selected to evaluate its potential as a chemopreventive agent.

Materials and methods: Alternative green solvents, powder-to-solvent ratios, and irradiation cycles were determined to optimize the MAE conditions. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to assess the cytotoxic effects against human breast cancer (MCF-7), liver cancer (HepG2), and mammary epithelium (hTert-HME1) cell lines.

Results: The extracts obtained from D-limonene and palm oil contained the highest concentrations of cannabidiol (CBD) and D-tetrahydrocannabinol (THC). A standardized D-limonene extract of cannabis (DEC) containing 0.03% w/w CBD and 1.37% w/w THC was selected for the evaluation of cytotoxic activity compared with CBD and THC. The results revealed that CBD and THC exhibited significant cytotoxic effects (p<0.05) against MCF-7 and HepG2, with the 50% inhibitory concentration (IC50) values of 18.5 and 12.37 μg/mL for CBD and 24.21 and 4.30 μg/mL for THC, respectively, whereas DEC exhibited moderate cytotoxicity against MCF-7 (IC50 of 488.85 μg/mL). However, CBD and THC exhibited significant cytotoxicity (p<0.05) against hTert-HME1 (IC50 values of 35.61 and 25.63 μg/mL, respectively), whereas DEC exhibited low cytotoxicity against hTert-HME1 (IC50 of 1.537.03 μg/mL).

Conclusion: DECs containing appropriate levels of THC and CBD have the potential to be candidates for cancer treatment. However, further investigations are required to improve the efficacy and safety profiles.”

https://pubmed.ncbi.nlm.nih.gov/40052396/

“The present study identified D-limonene and palm oil as promising alternative green solvents for extracting cannabinoids from cannabis inflorescences under MAE optimal conditions. The MAE method offers several advantages, including reduced time and energy consumption. In this study, DEC exhibited moderate cytotoxicity against MCF-7 cells with higher selectivity than CBD and THC. Therefore, DEC containing an appropriate amount of THC and CBD may exhibit a more satisfying anticancer effect and be a promising candidate for cancer treatment. However, additional research is required to understand the mechanisms of anticancer activity and to investigate additional efficacy and safety profiles.”

https://www.turkjps.org/articles/a-green-microwave-assisted-extraction-of-c-lessemgreatersativalessemgreater-l-extract-and-its-cytotoxic-activity-against-cancer-cells/doi/tjps.galenos.2025.33490

Association of Financial Wellness with Patterns of Medical Cannabis Use and Patient-Reported Outcomes in Adults with Cancer

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“Objective: Despite increasing use of medical cannabis to manage cancer-related symptoms, U.S. payers do not reimburse medical cannabis, leaving patients responsible for all associated costs. We assessed how self-reported financial well-being is associated with patterns of cannabis consumption, out-of-pocket costs, and impact on symptoms in patients with cancer.

Method: From December 2021 to January 2022, we surveyed patients with cancer enrolled in the Minnesota Medical Cannabis Program. The mailed survey included cancer history, cannabis use history, symptom changes and sociodemographic questions including income and perceived financial wellness. We conducted descriptive analyses.

Results: Of 797 eligible adults, 220 (28%) responded to the survey. Two hundred eleven answered a question about current household income as living comfortably (LC, 45%; n = 95) or not living comfortably (NLC, 55%; n = 116). The NLC group reported lower incomes (47% vs 8% with annual incomes <$50,000) and were typically younger, unmarried, unemployed, or disabled. NLC group purchased more vaporizers (48% vs 27%), used products high in THC (92% vs 82%), and reported higher cannabis costs (40% vs 21% spending $200+/month). The NLC group more often stopped or used cannabis less frequently than they would like (54% versus 32%), frequently citing costs as a reason (85% vs 39%). Both NLC and LC groups typically used cannabis daily and reported a high degree of symptom improvement.

Conclusions: Patients with cancer using cannabis report significant improvements in cancer-related symptoms. High out-of-pocket costs for cannabis may be especially burdensome among those already financially struggling, raising questions about affordability of and equitable access to this therapy.”

https://pubmed.ncbi.nlm.nih.gov/39968481/

https://publications.sciences.ucf.edu/cannabis/index.php/Cannabis/article/view/243

Combination of Cannabidiol with Cisplatin or Paclitaxel Analysis Using the Chou-Talalay Method and Chemo-Sensitization Evaluation in Platinum-Resistant Ovarian Cancer Cells

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“Background/Objectives: Cannabidiol (CBD) is known for its anti-cancer properties in preclinical models and is increasingly used alongside conventional chemotherapy in cancer treatment. This study aims to evaluate the anti-cancer activity of CBD from Lebanese Cannabis sativa as a monotherapy and in combination with cisplatin or paclitaxel on human ovarian adenocarcinoma cells. 

Methods: Cytotoxicity of CBD was tested on OVCAR-3 and SK-OV-3 cell lines using the MTS assay. The Chou-Talalay method and CompuSyn software were used to determine the combination indices (CIs) for predicting interactions between CBD and chemotherapeutic agents. CBD showed dose-dependent tumor growth inhibition at 72 h with comparable IC50 values for both cell lines. 

Results: The combination of CBD with cisplatin or paclitaxel showed significant antagonistic interaction in SK-OV-3 cells (CI > 1), but mild synergism (CI < 1) at high growth inhibition rates (95% and 97%) was observed in SK-OV-3 cells with CBD/cisplatin. Pure antagonism was found in OVCAR-3 cells with CBD/cisplatin. Priming SK-OV-3 cells with CBD reduced the IC50 values of both drugs significantly, with a similar effect seen when cells were primed with cisplatin or paclitaxel before CBD treatment. 

Conclusions: Integrating CBD with chemotherapy could improve cancer therapy and address drug resistance. Sequential administration of CBD and chemotherapeutic agents is more beneficial than simultaneous administration. Further in vivo studies are necessary to validate these findings and understand CBD’s interactions with other drugs fully.”

https://pubmed.ncbi.nlm.nih.gov/40002932/

“This study explores the anti-cancer activity of CBD, as monotherapy and in combination with two commonly used chemotherapeutic agents, cisplatin and paclitaxel, against platinum-resistant ovarian cancer OVCAR-3 and SK-OV-3 cell lines.

CBD monotherapy showed promising and significant tumor growth inhibitory effect against both cell lines. The current study demonstrated that the combination of CBD with cisplatin or paclitaxel displayed diminished inhibition of cell proliferation as compared to individual treatment.

CBD and paclitaxel exhibited an antagonistic interaction on all effect levels. In contrast, although antagonism was prominent over most of the inhibitory effect levels with concurrent treatment of CBD and cisplatin, synergy was detected at the highest effect levels, highlighting the potential benefit of combining the two agents at specific concentrations. However, priming with CBD, cisplatin, or paclitaxel has shown significant sensitization of SK-OV-3 cells to the subsequent treatment, stressing the importance of sequential, rather than simultaneous, administration of the drugs.

These findings offer valuable insights for optimizing current therapeutic options when integrating CBD with conventional chemotherapy by adopting priming regimens to circumvent the antagonism observed during co-treatment. Further investigations are necessary to validate the current results in vivo and elucidate the mechanism underlying the interaction of CBD with various anticancer drugs.”

https://www.mdpi.com/2227-9059/13/2/520

Tailored Iron Oxide Nanoparticles as Potential Cannabinoid Carriers for Anti-Cancer Treatment

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“We present a novel, multicomponent nanoparticulate carrier system based on superparamagnetic iron oxide nanoparticles with a designed hydrophilic/hydrophobic balance based on oleic acid and TWEEN 80 to incorporate hydrophobic cannabinoids-cannabigerol and cannabidiol-as well as the hydrophilic anthracycline drug epirubicin, forming a conjugate anticancer system.

Additionally, the superparamagnetic iron oxide-based nanoparticles formed the core of the system, thus providing it with magnetic hyperthermia capabilities with a specific absorption rate comparable to the corresponding systems in the literature. The interaction of the conjugate with the cell membrane was studied using the Langmuir monolayers at the air/water interface formed of selected lipids modeling the healthy and cancerous cell membranes.

Finally, cytotoxicity tests were carried out against the SKOV-3 cell line in vitro. A synergistic effect was observed when both the cannabinoid and epirubicin were present in the conjugate, as compared to the cannabinoid or epirubicin alone, making our system advantageous for further development for tentative therapeutic use.”

https://pubmed.ncbi.nlm.nih.gov/40001533/

https://www.mdpi.com/2218-273X/15/2/230

Extraction, GC-MS analysis, cytotoxic, anti-inflammatory and anticancer potential of Cannabis sativa female flower; in vitro, in vivo and in silico

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“This work examines the anticancer activity, the anti-inflammatory nature, and the cytotoxicity of the ethanol extract obtained from the female flowers of Cannabis sativa L using molecular methods in vitro, animal testing in vivo, as well as computational methods and simulations in silico.

From the GC-MS analysis, the following bioactive compounds were found: cannabidiol (CBD), tetrahydrocannabinol (THC), and humulene. The antiproliferative activities of the extract were determined on HeLa cells by using MTT, Crystal Violet, and Trypan Blue assays with an IC50 value suggesting 51%-77.6% lethality.

The bioinformatics analysis of molecular docking proved significant ligand-protein interactions of CBD, THC, and humulene with cancer-associated proteins such as PD-1/PD-L1, TNF-α, and MMP-9. In vivo, breast cancer was first established in female Sprague-Dawley rats with 7,12-dimethylbenz(a)anthracene (DMBA) then treated with cannabinoids either singularly or in combination.

Detailed treatment demonstrated that the use of the three cannabinoids simultaneously yielded the best anticancer and anti-inflammatory outcomes together with the best tumor reduction. The concentration of serum biomarkers of inflammation and tumor progression was substantially reduced in treated groups compared to the control group, which proves the synergistic effects of these cannabinoids in breast cancer therapy.

This study emphasizes the importance of medical Cannabis sativa derivatives in cancer treatment.”

https://pubmed.ncbi.nlm.nih.gov/40008130/

“Cancer still has no known treatment, and research is being conducted to create lead compounds and precursors that could be used as anticancer medications for 1 day. The goal of this study was to identify natural compounds with anticancer properties.

The MTT assay showed that cannabinoids retain anti-proliferative, anti-invasion, and apoptotic effects. IC50 upregulates 51%–77.6% of carcinoma cell death. The synergistic effects of cannabidiol, tetrahydrocannabinol, and humulene significantly suppressed PD-1/PD-L1 expression and oxidative stress, suggesting a possible approach for targeting breast cancer resistance. The greatest effect was obtained when all three compounds were combined, suggesting that the immunosuppressive and oxidative stress-modulatory effects of the compounds occurred synergistically.

Herein, we report comprehensive findings that may be helpful in designing new combinatory therapeutic strategies for breast cancer via the PD-1/PD-L1 pathway and oxidative stress markers. Further studies and trials are needed to identify more cannabinoid-based treatments and to combine pharmacological and cannabinoid drugs to gain remarkable effects against various cancer treatments.”

“Cannabis sativa is the oldest cultivated plant and contains a lot of naturally useful components used by humans. It is used as a source of fuel, food, herbal body care products, and medicines to cure different diseases. It is a plant of the Cannabaceae family. “

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1546062/full

Mechanisms of Cell Death Induced by Cannabidiol Against Tumor Cells: A Review of Preclinical Studies

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“Commonly known as marijuana or hemp, Cannabis sativa L. (Cannabaceae), contains numerous active compounds, particularly cannabinoids, which have been extensively studied for their biological activities. Among these, cannabidiol (CBD) stands out for its therapeutic potential, especially given its non-psychotropic effects.

This review evaluates the antitumor properties of CBD, highlighting its various mechanisms of action, including the induction of apoptosis, autophagy, and necrosis.

By synthesizing findings from in vitro studies on the cell death mechanisms and signaling pathways activated by CBD in various human tumor cell lines, this literature review emphasizes the therapeutic promise of this natural antineoplastic agent. We conducted a comprehensive search of articles in PubMed, Scopus, Springer, Medline, Lilacs, and Scielo databases from 1984 to February 2022.

Of the forty-three articles included, the majority (68.18%) reported that CBD activates apoptosis, while 18.18% observed simultaneous apoptosis and autophagy, 9.09% focused on autophagy alone, and 4.54% indicated necrosis. The antitumor effects of CBD appear to be mediated by transient receptor potential cation channels (TRPVs) in endometrial cancer, glioma, bladder cancer, and myeloma, with TRPV1, TRPV2, and TRPV4 playing key roles in activating apoptosis.

This knowledge paves the way for innovative therapeutic strategies that may enhance cancer treatment outcomes while minimizing the toxicity and side effects associated with conventional therapies.”

https://pubmed.ncbi.nlm.nih.gov/40006844/

“This review underscores the therapeutic potential of CBD as a promising antitumor agent across various cancer types, particularly through its interaction with transient receptor potential cation channels (TRPVs) and endocannabinoid CB receptors.

Our findings suggest that CBD primarily activates the apoptosis pathway while also engaging autophagy and necrosis, offering a multifaceted strategy for inducing cancer cell death. Moreover, the potential for combination therapies that integrate CBD with established chemotherapeutics highlights the importance of further research to investigate these synergies and optimize therapeutic regimens.

Although regulatory challenges persist, robust scientific evidence demonstrating CBD’s safety and efficacy of CBD will be crucial for advancing its clinical application in oncology.”

https://www.mdpi.com/2223-7747/14/4/585