“Breast cancer is the most commonly diagnosed cancer and a leading cause of cancer-related death among women worldwide. Somatostatin (SST) and Cannabinoids have an anti-proliferative and pro-apoptotic effect, but the mechanisms of their actions remain elusive.

In the present study, we have evaluated the effects of SST, Cannabidiol (CBD) alone or in combination on receptor expression, cell proliferation and apoptosis and related downstream signalling pathways in MDA-MB-231 and MCF-7 breast cancer cells.

The results presented here demonstrate the cell type and agonist-dependent changes in receptor expression at the cell membrane, inhibition of cell proliferation and increased apoptosis following treatment with SST and CBD alone and in combination. In comparison to MDA-MB-231 cells, MCF-7 cells treated with SST alone and in combination with CBD exhibited inhibition of phosphorylated Protein Kinase B (pAKT) and phosphorylated-Phosphoinositide 3-Kinase (pPI3K) expression. Importantly, inhibition of PI3K/AKT activation was accompanied by enhanced PTEN expression in MCF-7 cells.

These results highlight the possible interaction between SSTR and CBR subtypes with the implication in the modulation of receptor expression, cell viability and signal transduction pathways in a breast cancer cell type-dependent manner.”

https://pubmed.ncbi.nlm.nih.gov/36586156/

“Marijuana (or cannabis) is a source of large numbers of compounds known as phytocannabinoids, such as delta-9-tetrahydrocannabinol (Δ⁹-THC) and Cannabidiol (CBD) that have therapeutic implications in cancer, pain, inflammation and neurological diseases.”

https://www.sciencedirect.com/science/article/abs/pii/S0006291X22017442?via%3Dihub

“Epidermal growth factor receptor (EGFR) is a member of the ErbB family of proteins and are involved in downstream signal transduction, plays prominent roles in cell growth regulation, proliferation, and the differentiation of many cell types. They are correlated with the stage and severity of cancer. Therefore, EGFRs are targeted proteins for the design of new drugs to treat cancers that overexpress these proteins. Currently, several bioactive natural extracts are being studied for therapeutic purposes.

Cannabis has been reported in many studies to have beneficial medicinal effects, such as anti-inflammatory, analgesic, antibacterial, and anti-inflammatory effects, and antitumor activity. However, it is unclear whether cannabinoids reduce intracellular signaling by inhibiting tyrosine kinase phosphorylation. In this study, cannabinoids (CBD, CBG, and CBN) were simulated for binding to the EGFR-intracellular domain to evaluate the binding energy and binding mode based on molecular docking simulation.

The results showed that the binding site was almost always located at the kinase active site. In addition, the compounds were tested for binding affinity and demonstrated their ability to inhibit kinase enzymes. Furthermore, the compounds potently inhibited cellular survival and apoptosis induction in either of the EGFR-overexpressing cell lines.”

https://pubmed.ncbi.nlm.nih.gov/36568260/

“Cannabinoids reduced cell viability in EGFR-positive cells A431 and A549 by decreasing the tyrosine-kinase phosphorylation activity of EGFR.•

In silico analysis shows that cannabinoids bind to the active site of the EGFR-tyrosine kinase by the hydrophobic interaction and hydrogen bonding.•

CBD and CBG significantly induce cancer cells apoptosis in EGFR-positive cell A431.•

The consistent findings suggested that CBD and CBG could be developed as natural tumor-targeting agents for EGFR-positive cancers.

These findings demonstrate that the cannabinoids could be transformed into unique natural compounds for use in the development of anti-EGFR-positive cancer therapies.”

https://www.sciencedirect.com/science/article/pii/S2590257122000529?via%3Dihub

“Breast cancer is the main cancer type with more than 2.2 million cases in 2020, and is the principal cause of death in women; with 685000 deaths in 2020 worldwide. The estrogen receptor is involved at least in 70% of breast cancer diagnoses, and the agonist and antagonist properties of the drug in this receptor play a pivotal role in the control of this illness.

This work evaluated the agonist and antagonist mechanisms of 30 cannabinoids by employing molecular docking and dynamic simulations. Compounds with docking scores < -8 kcal/mol were analyzed by molecular dynamic simulation at 300 ns, and relevant insights are given about the protein’s structural changes, centered on the helicity in alpha-helices H3, H8, H11, and H12.

Cannabicitran was the cannabinoid that presented the best relative binding-free energy (-34.96 kcal/mol), and based on rational modification, we found a new natural-based compound with relative binding-free energy (-44.83 kcal/mol) better than the controls hydroxytamoxifen and acolbifen. Structure modifications that could increase biological activity are suggested.”

https://pubmed.ncbi.nlm.nih.gov/36543006/

https://www.sciencedirect.com/science/article/abs/pii/S0010482522011118?via%3Dihub

“The significant resistance to currently available chemotherapeutics makes treatment for TNBC a key clinical concern. Herein, we studied the anti-cancer potentials of synthetic cannabidiol (CBD) and Tetrahydrocannabivarin (THCV) when used alone or in combination with doxorubicin (DOX) against MDA-MB-231 resistant cells. Pre-treatment with CBD and THCV significantly increased the cytotoxicity of DOX in MDA-MB-231 2D and 3D cultures that were DOX-resistant. Transcriptomics and Proteomics studies revealed that CBD and THCV, by downregulating PD-L1, TGF-β, sp1, NLRP3, P38-MAPK, and upregulating AMPK induced apoptosis leading to improved DOX’s chemosensitivity against DOX resistant MDA-MB-231 tumors in BALB/c nude mice. CBD/THCV in combination with DOX significantly inhibited H3k4 methylation and H2K5 acetylation as demonstrated by western blotting and RT-PCR. Based on these findings, CBD and THCV appear to counteract histone modifications and their subsequent effects on DOX, resulting in chemo-sensitization against MDA-MB-231 resistant cancers.”

https://pubmed.ncbi.nlm.nih.gov/36535544/

“Cannabis anecdotally has been a folklore medicine for a longtime to treat a variety of disease states. In recent years, the therapeutic use of cannabis and cannabinoids has garnered more acceptance in the public domain. Several Phyto-cannabinoids are available from the the plant Cannabis sativa along with terpenes and they target the endocannabinoid system and several other biological pathways. Hence, these agents can possibly have a array of therapeutic effects on the central nervous system and peripheral immune, cardiovascular, reproductive, and ocular systems.

Our findings show that CBD and THCV were found to overcome resistance against MDA-MB-231 resistant cell line in vitro in 2D and 3D cultures by several folds. Further, both these agents in combination with DOX showed synergism as determined by the isobolographic method.”

https://www.sciencedirect.com/science/article/abs/pii/S0300908422003327?via%3Dihub