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

Posted on June 20, 2014 by David

“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

Posted on June 5, 2014 by David

“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.

A 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.

Posted on March 31, 2014 by David

“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.

Posted on March 31, 2014 by David

“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.

Posted on March 31, 2014 by David

“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.

Posted on March 1, 2014 by David

Image result for current opinion in clinical nutrition & metabolic care

“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.

Posted on March 1, 2014 by David

“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

Knocking down the expression of adenylate cyclase-associated protein 1 inhibits the proliferation and migration of breast cancer cells.

Posted on February 27, 2014 by David

“Adenylate cyclase-associated protein 1 (CAP1) is a conserved protein that was found to be up-regulated in breast cancer and related to the migration of breast cancer…

CAP1 might be a potential molecular targeted therapy for surgery and immune treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/24509166

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

Inhibition of adenylate cyclase by delta 9-tetrahydrocannabinol in mouse spleen cells: a potential mechanism for cannabinoid-mediated immunosuppression.

Posted on February 27, 2014 by David

“The ability of delta 9-Tetrahydrocannabinol (delta 9-THC) to modulate adenylate cyclase activity in mouse spleen cells was investigated…

delta 9-THC treated spleen cells demonstrated a 33% inhibition and a 66% inhibition in intracellular cAMP… respectively…

These studies suggest that inhibition of immune function by delta 9-THC may be mediated through the inhibition of intracellular cAMP early after antigen stimulation.”

http://www.ncbi.nlm.nih.gov/pubmed/1321935

Anandamide, a naturally-occurring agonist of the cannabinoid receptor, blocks adenylate cyclase at the frog neuromuscular junction.

Posted on February 27, 2014 by David

“Anandamide (arachydonylethanolamide) is a naturally-occurring ligand of the canabinoid receptor. When anandamide binds to its receptor, adenylate cyclase is inhibited…

The conclusions are that the motor nerve terminal has a cannabinoid receptor.

The binding of anandamide to this receptor seems to block adenylate cyclase.”

http://www.ncbi.nlm.nih.gov/pubmed/7953630