Δ(9)-tetrahydrocannabinol targeting estrogen receptor signaling: the possible mechanism of action coupled with endocrine disruption.

“Δ(9)-Tetrahydrocannabinol (Δ(9)-THC), a biologically active constituent of marijuana, possesses a wide variety of pharmacological and toxicological effects (e.g., analgesia, hypotension, reduction of inflammation, and anti-cancer effects).

Among Δ(9)-THC’s biological activities, its recognized anti-estrogenic activity has been the subject of investigations.

… Δ(9)-THC is used as both a drug of abuse (marijuana) and as a preventive therapeutic to treat pain and nausea in cancer patients undergoing chemotherapy…

…important to investigate the mechanistic basis underlying the anti-estrogenic activity of Δ(9)-THC…

We have recently reported that ERβ, a second type of ER, is involved in the Δ(9)-THC abrogation of E2/ERα-mediated transcriptional activity. Here we discuss the possible mechanism(s) of the Δ(9)-THC-mediated disruption of E2/ERα signaling by presenting our recent findings as well.”

http://www.ncbi.nlm.nih.gov/pubmed/25177025

 

Down-regulation of cyclooxygenase-2 (COX-2) by cannabidiolic acid in human breast cancer cells.

“Metastases are known to be responsible for approximately 90% of breast cancer-related deaths.

Cyclooxygenase-2 (COX-2) is involved not only in inflammatory processes, but also in the metastasis of cancer cells…

…cannabidiolic acid (CBDA), a selective COX-2 inhibitor found in the fiber-type cannabis plant…

Taken together, the results obtained here demonstrated that i) CBDA had dual inhibitory effects on COX-2 through down-regulation and enzyme inhibition, and ii) CBDA may possess the ability to suppress genes that are positively involved in the metastasis of cancer cells in vitro.”

http://www.ncbi.nlm.nih.gov/pubmed/25242400

“Cannabidiolic acid as a selective cyclooxygenase-2 inhibitory component in cannabis…Taken together, these lines of evidence in this study suggest that naturally occurring CBDA in cannabis is a selective inhibitor for COX-2.”  http://dmd.aspetjournals.org/content/36/9/1917.long

“Cannabidiolic acid, a major cannabinoid in fiber-type cannabis, is an inhibitor of MDA-MB-231 breast cancer cell migration… The data presented in this report suggest for the first time that as an active component in the cannabis plant, CBDA offers potential therapeutic modality in the abrogation of cancer cell migration, including aggressive breast cancers.”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4009504/

http://www.thctotalhealthcare.com/category/breast-cancer/

Cannabinoid CB2 Receptor as a New Phototherapy Target for the Inhibition of Tumor Growth.

“The success of targeted cancer therapy largely relies upon the selection of target and the development of efficient therapeutic agents that specifically bind to the target. In the current study, we chose a cannabinoid CB2 receptor (CB2R) as a new target and used a CB2R-targeted photosensitizer, IR700DX-mbc94, for phototherapy treatment…

Taken together, IR700DX-mbc94 is a promising phototherapy agent with high target-specificity. Moreover, CB2R appears to have great potential as a phototherapeutic target for cancer treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/24779700

“Target-selective phototherapy using a ligand-based photosensitizer for type 2 cannabinoid receptor. Phototherapy is a powerful, noninvasive approach for cancer treatment, with several agents currently in clinical use… We show that our CB2R-targeted phototherapy agent, IR700DX-mbc94, is specific for CB2R and effective only when bound to the target receptor. Overall, this opens up the opportunity for development of an alternative treatment option for CB2R-positive cancers.”  http://www.ncbi.nlm.nih.gov/pubmed/24583052

Targeting multiple cannabinoid antitumor pathways with a resorcinol derivative leads to inhibition of advanced stages of breast cancer.

“The psychoactive cannabinoid Δ9 -tetrahydrocannabinol (THC) and the non-psychoactive cannabinoid cannabidiol(CBD) can both reduce cancer progression each through distinct antitumor pathways.

Our goal was to discover a compound that could efficiently target both cannabinoid antitumor pathways.

KEY RESULTS:

CBD reduced breast cancer metastasis in advanced stages of the disease as the direct result of down-regulating the transcriptional regulator Id1. However, this was associated with moderate increases in survival. We therefore screened for analogs that could co-target cannabinoid antitumor pathways (CBD- and THC-associated) and discovered the compound O-1663. This analog inhibited Id1, produced a marked stimulation of ROS, upregulated autophagy, and induced apoptosis. Of all compounds tested, it was the most potent at inhibiting breast cancer cell proliferation and invasion in culture and metastasis in vivo.

CONCLUSIONS AND IMPLICATIONS:

O-1663 prolonged survival in advanced stages of breast cancer metastasis. Developing compounds that can simultaneously target multiple cannabinoid antitumor pathways efficiently may provide a novel approach for the treatment of patients with metastatic breast cancer.”

http://www.ncbi.nlm.nih.gov/pubmed/24910342

“Anti-cancer effects of resorcinol derivatives on ascitic and solid forms of Ehrlich carcinoma in mice.” http://www.ncbi.nlm.nih.gov/pubmed/13774935

“Ardisiphenol D, a resorcinol derivative identified from Ardisia brevicaulis, exerts antitumor effect through inducing apoptosis in human non-small-cell lung cancer A549 cells.” http://www.ncbi.nlm.nih.gov/pubmed/24392814

“Antitumor effect of resorcinol derivatives from the roots of Ardisia brevicaulis by inducing apoptosis.” http://www.ncbi.nlm.nih.gov/pubmed/21751842

“Resorcinol derivatives from Ardisia maculosa.”  http://www.ncbi.nlm.nih.gov/pubmed/17885843

“Cannabidiol (CBD) is among the major secondary metabolites of Cannabis devoid of the delta-9-tetra-hydrocannabinol psychoactive effects. It is a resorcinol-based compound with a broad spectrum of potential therapeutic properties, including neuroprotective effects in numerous pathological conditions.” https://www.ncbi.nlm.nih.gov/pubmed/28412918

http://www.thctotalhealthcare.com/category/breast-cancer/

Cannabidiol (CBD) Shown To Kill Breast Cancer Cells -Cafemom

“Cannabidiol (CBD) has been on the receiving end of a lot of attention from the scientific community for several decades now.

However, it is only now that we are really starting to begin to get a grasp on how wonderful this cannabinoid truly is.

study from 2011 states that cannabidiol is considered an antineoplastic agent on the basis of its in vitro and in vivo activity against tumor cells. However, the exact molecular mechanism through which CBD works in this capacity is yet to be understood. The study, titled “Cannabidiol Induces Programmed Cell Death in Breast Cancer Cells by Coordinating the Cross-talk between Apoptosis and Autophagy,” focuses on how CBD can kill breast cancer cells. Breast cancer is the second leading cause of cancer-related death in women in the United States.

What the scientists found was that CBD influences apoptosis by interacting with a key protein, called beclin-1, found within the cancerous cell. Beclin-1 is also known to play a key role in autophagy, or cellular self-degradation of non-vital components, which may lead to programmed cell death. This causes a distortion of the electrical signals between the outer mitochondrial membrane and the rest of the cell, disrupting the transfer to the cell interior of certain molecules that are necessary for metabolism. What this means is that the cell cannot transfer energy, and the cell starves to death, and in doing so activates the self-destruction process of apoptosis.

The study concludes by stating, “In summary, we showed that CBD, a plant-derived cannabinoid, preferentially kills breast cancer cells by inducing ER stress, inhibiting mTOR signaling, enhancing ROS generation, and mediating a complex balance between autophagy and mitochondria-mediated apoptosis in MDA-MB-231 breast cancer cells. These findings support the continued exploration of CBD as an alternative agent for breast cancer treatment.””

http://www.cafemom.com/group/99198/forums/read/19190923/Cannabidiol_CBD_Shown_To_Kill_Breast_Cancer_Cells

“Cannabidiol Induces Programmed Cell Death in Breast Cancer Cells by Coordinating the Cross-talk between Apoptosis and Autophagy… In summary, we showed that CBD, a plant-derived cannabinoid, preferentially kills breast cancer cells…” http://mct.aacrjournals.org/content/10/7/1161.full

http://www.thctotalhealthcare.com/category/breast-cancer/

Characterization of the structural determinants required for potent mechanism-based inhibition of human cytochrome P450 1A1 by cannabidiol.

“We previously demonstrated that cannabidiol (CBD) was a potent mechanism-based inhibitor of human cytochrome P450 1A1 (CYP1A1)…

These results suggest that the methylresorcinol structure in CBD may have structurally important roles in the inactivation of CYP1A1.”

http://www.ncbi.nlm.nih.gov/pubmed/24667653

“CYP1A1 regulates breast cancer proliferation and survival. This study supports the notion that CYP1A1 promotes breast cancer proliferation and survival… reduction of CYP1A1 levels is a potential strategy for breast cancer therapeutics.”  http://www.ncbi.nlm.nih.gov/pubmed/23576571

Structural requirements for potent direct inhibition of human cytochrome P450 1A1 by cannabidiol: role of pentylresorcinol moiety.

“Our recent work has shown that cannabidiol (CBD) exhibits the most potent direct inhibition of human cytochrome P450 1A1 (CYP1A1)…

These results suggest that the pentylresorcinol structure in CBD may have structurally important roles in direct CYP1A1 inhibition, although the whole structure of CBD is required for overall inhibition.”

http://www.ncbi.nlm.nih.gov/pubmed/23811569

“CYP1A1 regulates breast cancer proliferation and survival. This study supports the notion that CYP1A1 promotes breast cancer proliferation and survival… reduction of CYP1A1 levels is a potential strategy for breast cancer therapeutics.”  http://www.ncbi.nlm.nih.gov/pubmed/23576571

Characterization of major phytocannabinoids, cannabidiol and cannabinol, as isoform-selective and potent inhibitors of human CYP1 enzymes.

“Inhibitory effects of Delta(9)-tetrahydrocannabinol (Delta(9)-THC), cannabidiol (CBD), and cannabinol (CBN), the three major constituents in marijuana, on catalytic activities of human cytochrome P450 (CYP) 1 enzymes were investigated.

These results indicated that CBD and CBN showed CYP1 isoform-selective direct inhibition and that CBD was characterized as a potent mechanism-based inhibitor of human CYP1 enzymes, especially CYP1A1.”

http://www.ncbi.nlm.nih.gov/pubmed/20117100

“CYP1A1 regulates breast cancer proliferation and survival. This study supports the notion that CYP1A1 promotes breast cancer proliferation and survival… reduction of CYP1A1 levels is a potential strategy for breast cancer therapeutics.”  http://www.ncbi.nlm.nih.gov/pubmed/23576571

Endocannabinoid system in cancer cachexia.

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“More than 60% of advanced cancer patients suffer from anorexia and cachexia.

This review focuses on the possible mechanisms by which the endocannabinoid system antagonizes cachexia-anorexia processes in cancer patients and how it can be tapped for therapeutic applications.

Cannabinoids stimulate appetite and food intake…

Cannabinoid type 1 receptor activation stimulates appetite and promotes lipogenesis and energy storage.

Further study of cancer-cachexia pathophysiology and the role of endocannabinoids will help us to develop cannabinoids without psychotropic properties, which will help cancer patients suffering from cachexia and improve outcomes of clinical antitumor therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/17563462

The endocannabinoid signaling system in cancer.

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“The endocannabinoid system, comprising lipid-derived endocannabinoids, their G-protein-coupled receptors (GPCRs), and the enzymes for their metabolism, is emerging as a promising therapeutic target in cancer.

This report highlights the main signaling pathways for the antitumor effects of the endocannabinoid system in cancer and its basic role in cancerpathogenesis, and discusses the alternative view of cannabinoid receptors as tumor promoters.

We focus on new players in the antitumor action of the endocannabinoid system and on emerging crosstalk among cannabinoid receptors and other membrane or nuclear receptors involved in cancer.”

http://www.ncbi.nlm.nih.gov/pubmed/23602129