“Colorectal cancer (CRC), found in the intestinal tract, is initiated and progresses through various mechanisms, including the dysregulation of signaling pathways. Several signaling pathways, such as EGFR and MAPK, involved in cell proliferation, migration, and apoptosis, are often dysregulated in CRC.

Although cannabidiol (CBD) has previously induced apoptosis and cell cycle arrest in vitro in CRC cell lines, its effects on signaling pathways have not yet been determined. An in silico analysis was used here to assess partner proteins that can bind to CBD, and docking simulations were used to predict precisely where CBD would bind to these selected proteins. A survey of the current literature was used to hypothesize the effect of CBD binding on such proteins.

The results predict that CBD could interact with EGFR, RAS/RAF isoforms, MEK1/2, and ERK1/2. The predicted CBD-induced inhibition might be due to CBD binding to the ATP binding site of the target proteins. This prevents the required phosphoryl transfer to activate substrate proteins and/or CBD binding to the DFG motif from taking place, thus reducing catalytic activity.”

https://pubmed.ncbi.nlm.nih.gov/39194723/

“This in silico study predicts that CBD could play a pivotal role in inhibiting the EGFR and MAPK pathways since almost all the proteins involved in this pathway interact with CBD. The most notable interactions occur between CBD and EGFR, KRAS, BRAF, and MEK1, as reflected by docking scores and being the most critically mutated or dysregulated proteins in colorectal cancer. CBD is proposed to act as an inhibitor of these proteins mainly by binding to the ATP catalytic binding site, which prevents phosphotransfer and the subsequent downstream activation of the substrate proteins. Secondly, CBD can act by binding to the DFG, which is adjacent to the hydrophobic pocket. The catalytic activity of this target protein is inhibited by this mechanism. Since the effect of CBD on these proteins has not yet been investigated, future studies should aim to determine if CBD indeed binds to these predicted target sites in these proteins and if the expected inhibitory effect occurs. Furthermore, in vitro phosphorylation studies on the selected proteins may determine if the phosphorylation of these proteins is affected by CBD treatment. In conclusion, CBD is predicted to interact with multiple role-players in the EGFR and MAPK pathways, potentially inhibiting these pathways and proteins.”

https://www.mdpi.com/1467-3045/46/8/506

“This study investigates the phytochemical composition and biological activities of hemp (Cannabis sativa L.) leaves, flowers’ methanolic extracts from the Sofia variety, and its sprouts cultivated under different light conditions (natural light, darkness, blue, and white LED light for 5, 7, and 9 days).

Phytochemical analysis using HPLC identified four key polyphenolic compounds in sprouts’ extracts: chlorogenic, caffeic, and gallic acids, and myricetin, with a predomination of the chlorogenic acid. In contrast, leaves and flowers’ extracts contained cannflavins A and B and chlorogenic, p-coumaric, and ferulic acids, with a significant presence of isochlorogenic acid. Antioxidant capacity, assessed by FRAP method, revealed higher antioxidant potential in leaves compared to flowers and sprouts, with sprouts grown under blue and white LED lights exhibiting the highest activity.

Cytotoxic activity was evaluated on human colon cancer cell lines (HT29, HCT116, DLD-1) and normal colon epithelial cells (CCD 841 CoN).

Results demonstrated significant and selective cytotoxicity against cancer cell lines, with leaves showing more pronounced effects than flowers, and sprouts only moderate activity. All samples revealed an anti-inflammatory effect in vitro.

To conclude, sprouts, leaves, and flowers of the Sofia hemp may be considered promising products for chemoprevention in the future.”

https://pubmed.ncbi.nlm.nih.gov/39124141/

“Cannabis sativa L. is a species of Asian origin that has been cultivated since ancient times for commercial, nutritional, and medicinal purposes.

The results indicate the interesting chemopreventive potential of sprouts, leaves, and flowers from Sofia hemp variety, manifested as cytotoxic, antioxidant, and anti-inflammatory activity.”

https://www.mdpi.com/2223-7747/13/15/2023

“Cannabis sativa L., with a rich history in Chinese folk medicine, includes hemp strains that offer substantial economic and medical benefits due to their non-addictive properties.

Hemp has demonstrated various pharmaceutical activities, including anti-inflammatory, antioxidant, and anti-tumor effects.

This study explores the potential of hemp oil extract (HOE) in treating colorectal cancer (CRC). Despite its promise, the specific anticancer mechanisms of HOE have not been well understood. To elucidate these mechanisms, we employed mass spectrometry-based metabolomics and proteomics to investigate the global effects of HOE on CRC cells. Additionally, bioinformatics approaches, including bulk RNA-seq and single-cell RNA-seq, were used to identify gene expression differences and cellular heterogeneity. The results were validated using flow cytometry, western blotting, and immunohistochemistry.

Our findings reveal that HOE induces significant alterations in purine metabolism pathways, down-regulates c-MYC, and inhibits the expression of cell cycle-related proteins such as CCND1, CDK4, and CDK6, leading to cell cycle arrest in the G1 phase. This comprehensive analysis demonstrates that HOE effectively blocks the cell cycle in the G1 phase, thereby inhibiting colorectal cancer cell proliferation.

These findings provide experimental evidence supporting the potential therapeutic use of hemp in medicine.”

https://pubmed.ncbi.nlm.nih.gov/39059180/

“HOE effectively suppressed CRC cell proliferation both in vitro and in vivo.”

https://www.sciencedirect.com/science/article/abs/pii/S0731708524004199?via%3Dihub

“Phytocannabinoids, compounds found in Cannabis sativa L., are used in oncology and palliative care to reduce the adverse reactions of standard therapies. Cancer patients use formulations of Cannabis sativa L. to manage the anxiety, pain, and nausea associated with cancer treatment, and there is growing evidence that some of them may exhibit anticancer properties.

In this study, we tested the anticancer potential of selected cannabinoids CBD (cannabidiol) and its quinone derivative CBD-HQ (cannabidiol hydroquinone), CBG (cannabigerol) and its acid derivative CBG-A (cannabigerolic acid), as well as a combination of CBD+CBG on the colon cancer cell line SW-620.

The MTT assay was used to determine the cannabinoids’ ability to induce colon cancer cell death. All cannabinoids were cytotoxic at the lowest concentration (3 μg/mL). The half maximal inhibitory concentration (IC50) ranged from 3.90 to 8.24 μg/mL, depending on the substance. Cytotoxicity was confirmed in a 3D spheroidal cell culture with calcein and propidium iodide staining. The amount of intracellular reactive oxygen species (ROS) was examined using a DCF-DA assay. CBG showed the lowest antioxidant activity of all the cannabinoids tested. The level of intracellular ROS decreased only by 0.7-18%. However, CBG-A induced the strongest reduction in ROS level by 31-39%.

Our results suggest that cannabinoids represent an interesting research direction with great implementation potential. These preliminary results represent the beginning of research into the potential of these substances for anticancer treatment and underscore the potential for further research.”

https://pubmed.ncbi.nlm.nih.gov/38666957/

“There is no doubt that phytocannabinoids represent an interesting research direction with great potential for implementation.”

https://www.mdpi.com/1467-3045/46/4/227

“The evolution of regulatory perspectives regarding the health and nutritional properties of industrial hemp-based products (Cannabis sativa L.) has pushed research to focus on the development of new methods for both the extraction and formulation of the bioactive compounds present in hemp extracts. While the psychoactive and medicinal properties of hemp-derived cannabinoid extracts are well known, much less has been investigated on the functional and antimicrobial properties of hemp extracts.

Within the hemp value chain, various agricultural wastes and by-products are generated. These materials can be valorised through eco-innovations, ultimately promoting sustainable economic development. In this study, we explored the use of waste from industrial light cannabis production for the extraction of bioactive compounds without the addition of chemicals. The five extracts obtained were tested for their antimicrobial activity on both planktonic and sessile cells of pathogenic strains of the Candida albicans, Candida parapsilosis, and Candida tropicalis species and for their antioxidant activity on HT-29 colon cancer cells under oxidative stress.

Our results demonstrated that these extracts display interesting properties both as antioxidants and in hindering the development of fungal biofilm, paving the way for further investigations into the sustainable valorisation of hemp waste for different biomedical applications.”

https://pubmed.ncbi.nlm.nih.gov/38612793/

https://www.mdpi.com/1422-0067/25/7/3979

“Chemotherapy resistance is an insurmountable problem in clinical anticancer therapy. Although Oxaliplatin is an effective chemotherapeutic agent for the treatment of colorectal cancer (CRC), it still suffers from serious toxicities as well as drug resistance. In this work, three Oxaliplatin tetravalent platinum prodrugs(O1-O3) and three novel mixed ammine/amine analogs(C1-C3) were constructed, introducing cannabidiol with anti-tumor activity in their axial position.

All Pt(IV) prodrugs exhibited potent antitumor effects in a variety of tumor cell lines, especially in HCT-116 cells, where complex O3 showed strong inhibitory effects with the half maximal inhibitory concentrations (IC₅₀) value of 6.02 ± 0.69 μM and about 2.6 times higher than that of Oxaliplatin. Further studies revealed that complex O3 decreased cellular mitochondrial membrane potential in a concentration-dependent manner and enhanced reactive oxygen species (ROS) accumulation by decreasing the expression of catalase, superoxide dismutase 2 (SOD2) and superoxide dismutase 3 (SOD3). Complex O3 induces mitochondrial dysfunction and upregulates the pro-apoptotic protein Noxa, ultimately leading to severe DNA damage. The upregulation of Phosphorylated histone protein H2AX (γ-H2AX) expression is clear evidence. In addition, O3 inhibits the expression of RAD51 protein and prevents DNA damage repair, thus overcoming drug resistance.

This strategy of combining bioactive molecules cannabidiol with platinum drugs to improve therapeutic efficacy and overcome drug resistance has been proven to be very effective and deserves further investigation.”

https://pubmed.ncbi.nlm.nih.gov/38490045/

“The cannabidiol was introduced into the platinum antitumor drugs, and the Pt(IV) complexes O1-O3 and C1- C3 were synthesized.

•Complex O3 is highly cytotoxic to all cancer cells and cannabidiol exerts a synergistic antitumor effect with Oxaliplatin.”

https://www.sciencedirect.com/science/article/abs/pii/S0162013424000382?via%3Dihub