Cannabidiol-from Plant to Human Body: A Promising Bioactive Molecule with Multi-Target Effects in Cancer.

 ijms-logo“Cannabis sativa L. is a plant long used for its textile fibers, seed oil, and oleoresin with medicinal and psychoactive properties. It is the main source of phytocannabinoids, with over 100 compounds detected so far. In recent years, a lot of attention has been given to the main phytochemicals present in Cannabis sativa L., namely, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). Compared to THC, CBD has non-psychoactive effects, an advantage for clinical applications of anti-tumor benefits. The review is designed to provide an update regarding the multi-target effects of CBD in different types of cancer. The main focus is on the latest in vitro and in vivo studies that present data regarding the anti-proliferative, pro-apoptotic, cytotoxic, anti-invasive, anti-antiangiogenic, anti-inflammatory, and immunomodulatory properties of CBD together with their mechanisms of action. The latest clinical evidence of the anticancer effects of CBD is also outlined. Moreover, the main aspects of the pharmacological and toxicological profiles are given.”

https://www.ncbi.nlm.nih.gov/pubmed/31775230

https://www.mdpi.com/1422-0067/20/23/5905

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Cannabinoid WIN 55,212-2 induces cell cycle arrest and apoptosis, and inhibits proliferation, migration, invasion, and tumor growth in prostate cancer in a cannabinoid-receptor 2 dependent manner.

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“Cannabinoids have demonstrated anticarcinogenic properties in a variety of malignancies, including in prostate cancer.

In the present study, we explored the anti-cancer effects of the synthetic cannabinoid WIN 55,212-2 (WIN) in prostate cancer.

RESULTS:

WIN significantly reduced prostate cancer cell proliferation, migration, invasion, induced apoptosis, and arrested cells in Go/G1 phase in a dose-dependent manner. Mechanistic studies revealed these effects were mediated through a pathway involving cell cycle regulators p27, Cdk4, and pRb. Pre-treatment with a CB2 antagonist, AM630, followed by treatment with WIN resulted in a reversal of the anti-proliferation and cell cycle arrest previously seen with WIN alone. In vivo, administration of WIN resulted in a reduction in the tumor growth rate compared to control (P < 0.05).

CONCLUSIONS:

The following study provides evidence supporting the use of WIN as a novel therapeutic for prostate cancer.”

https://www.ncbi.nlm.nih.gov/pubmed/30242861

https://onlinelibrary.wiley.com/doi/abs/10.1002/pros.23720

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Assessment of Cannabinoids Agonist and Antagonist in Invasion Potential of K562 Cancer Cells

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“The prominent hallmark of malignancies is the metastatic spread of cancer cells. Recent studies have reported that the nature of invasive cells could be changed after this phenomenon, causing chemotherapy resistance.

It has been demonstrated that the up-regulated expression of matrix metalloproteinase (MMP) 2/MMP-9, as a metastasis biomarker, can fortify the metastatic potential of leukemia.

Furthermore, investigations have confirmed the inhibitory effect of cannabinoid and endocannabinoid on the proliferation of cancer cells in vitro and in vivo.

Our findings clarifies that CB1 receptors are responsible for anti-invasive effects in the K562 cell line.”

https://www.ncbi.nlm.nih.gov/pubmed/29883990

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Anti-invasion Effects of Cannabinoids Agonist and Antagonist on Human Breast Cancer Stem Cells.

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“Studies show that cancer cell invasion or metastasis is the primary cause of death in malignancies including breast cancer.

The existence of cancer stem cells (CSCs) in breast cancer may account for tumor initiation, progression, and metastasis.

Recent studies have reported different effects of cannabinoids on cancer cells via CB1 and CB2 cannabinoid receptors.

In the present study, the effects of ACEA (a selective CB1 receptor agonist) and AM251 (a selective CB1 antagonist) on CSCs and their parental cells were investigated.

It was observed that ACEA decreased CD44+/CD24-/low/ESA+ cancer stem cell invasiveness.

Since one of the main cancer recurrence factors is anti-cancer drugs fail to inhibit CSC population, this observation would be useful for cancer treatment.”

https://www.ncbi.nlm.nih.gov/pubmed/29552056

“Our results indicate that cannabinoids may interfere with invasive cancer stem cells in benefit of cancer eradication. In summary, our results clarified that cannabinoid receptor agonist possesses anti-invasion potential in both main population and breast cancer stem cells. Considering that most anti-cancer drugs do not eradicate stem cells and only target main population cells, the results disclosed here can be used for prevention of cancer recurrence.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5843309/

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WIN 55,212-2 Inhibits the Epithelial Mesenchymal Transition of Gastric Cancer Cells via COX-2 Signals.

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“Cannabinoids (the active components of Cannabis sativa) and their derivatives have received considerable interest due to reports that they can affect the tumor growth, migration, and metastasis.

Previous studies showed that the cannabinoid agonist WIN 55,212-2 (WIN) was associated with gastric cancer (GC) metastasis, but the mechanisms were unknown.

RESULTS:

WIN inhibited cell migration, invasion, and epithelial to mesenchymal transition (EMT) in GC. WIN treatment resulted in the downregulation of cyclooxygenase-2 (COX-2) expression and decreased the phosphorylation of AKT, and inhibited EMT in SGC7901 cells. Decreased expression of COX-2 and vimentin, and increased expression of E-cadherin, which was induced by WIN, were normalized by overexpression of AKT, suggesting that AKT mediated, at least partially, the WIN suppressed EMT of GC cells.

CONCLUSION:

WIN can inhibit the EMT of GC cells through the downregulation of COX-2.”

https://www.ncbi.nlm.nih.gov/pubmed/27802436

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Antitumorigenic targets of cannabinoids – current status and implications.

“Molecular structures of the endocannabinoid system have gained interest as potential pharmacotherapeutical targets for systemic cancer treatment.

The present review covers the contribution of the endocannabinoid system to cancer progression. Particular focus will be set on the accumulating preclinical data concerning antimetastatic, anti-invasive and anti-angiogenic mechanisms induced by cannabinoids.

Expert opinion: The main goal of targeting endocannabinoid structures for systemic anticancer treatment is the comparatively good safety profile of cannabinoid compounds.

In addition, antitumorigenic mechanisms of cannabinoids are not restricted to a single molecular cascade but involve multiple effects on various levels of cancer progression such as angiogenesis and metastasis. Particularly the latter effect has gained interest for pharmacological interventions.

Thus, drugs aiming at the endocannabinoid system may represent potential “antimetastatics” for an upgrade of a future armamentarium against cancer diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/27070944

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

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The antitumor action of cannabinoids on glioma tumorigenesis.

“Cannabinoids are a class of chemical compounds with a wide spectrum of pharmacological effects, mediated by two specific plasma membrane receptors (CB1 and CB2).

Recently, CB1 and CB2 expression levels have been detected in human tumors, including those of brain.

Cannabinoids-endocannabinoids exert anti-inflammatory, anti-proliferative, anti-invasive, anti-metastatic and pro-apoptotic effects in different cancer types, both in vitro and in vivo in animal models, after local or systemic administration.

We present the available experimental and clinical data, to date, regarding the antitumor action of cannabinoids on the tumorigenesis of gliomas.”

http://www.ncbi.nlm.nih.gov/pubmed/25472761

http://www.thctotalhealthcare.com/category/gllomas/

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Cannabinoids as therapeutic agents in cancer: current status and future implications

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“Cannabinoids… active compounds of the Cannabis sativa plant… cannabinoids are clinically used for anti-palliative effects, recent studies open a promising possibility as anti-cancer agents.

They have been shown to possess anti-proliferative and anti-angiogenic effects in vitro as well as in vivo in different cancer models…”  http://www.ncbi.nlm.nih.gov/pubmed/25115386

“Cannabinoids… the active compounds of the Cannabis sativa plant… anti-cancer agents… anti-proliferative… anti-angiogenic… anti-migratory and anti-invasive… The administration of single cannabinoids might produce limited relief compared to the administration of crude extract of plant containing multiple cannabinoids, terpenes and flavanoids.” Full-text: http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B0%5D=2233&path%5B1%5D=3664

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

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CANNABINOIDS INCREASE LUNG CANCER CELL LYSIS BY LYMPHOKINE-ACTIVATED KILLER CELLS VIA UPREGULATION OF ICAM-1.

“Cannabinoids have been shown to promote the expression of the intercellular adhesion molecule 1 (ICAM-1) on lung cancer cells as part of their anti-invasive and antimetastatic action…

Cannabidiol (CBD), a non-psychoactive cannabinoid, enhanced the susceptibility of cancer cells to adhere to and subsequently lysed by LAK cells, with both effects being reversed by a neutralizing ICAM-1 antibody…

ICAM-1-dependent pro-killing effects were further confirmed for the phytocannabinoid Δ9-tetrahydrocannabinol (THC) and R(+)-methanandamide, a stable endocannabinoid analogue…

Altogether, our data demonstrate cannabinoid-induced upregulation of ICAM-1 on lung cancer cells to be responsible for increased cancer cell susceptibility to LAK cell-mediated cytolysis.

These findings provide proof for a novel antitumorigenic mechanism of cannabinoids.”

http://www.ncbi.nlm.nih.gov/pubmed/25069049

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

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Study: Marijuana Appears to Slow Cancer Growth in Laboratory Setting -FOXNEWS

“Certain marijuana components may suppress the tumors of highly invasive cancers, a new study finds.

In laboratory tests, cannabinoids, the active components in marijuana, were found to slow the spread of lung and cervical cancer tumors, according to researchers Robert Ramer and Burkhard Hinz of the University of Rostock in Germany.

Proponents of medical marijuana believe that cannabinoids reduce the side effects of cancer treatment, such as pain, weight loss and vomiting.

The study, published in the Jan. 2 issue of the Journal of the National Cancer Institute, finds that the compounds may also have an anticancer effect;

Click here for the study.

In addition to suppressing tumor cell invasion, cannabinoids also stimulated the expression of TIMP-1, an inhibitor of a group of enzymes involved in tumor cell invasion.

“To our knowledge, this is the first report of TIMP-1-dependent anti-invasive effects of cannabinoids,” the authors wrote. “This signaling pathway may play an important role in the antimetastatic action of cannabinoids, whose potential therapeutic benefit in the treatment of highly invasive cancers should be addressed in clinical trials.””

https://www.foxnews.com/story/study-marijuana-appears-to-slow-cancer-growth-in-laboratory-setting

“Inhibition of Cancer Cell Invasion by Cannabinoids via Increased Expression of Tissue Inhibitor of Matrix Metalloproteinases-1. Cannabinoids may therefore offer a therapeutic option in the treatment of highly invasive cancers.” https://academic.oup.com/jnci/article/100/1/59/2567700

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