Category Archives: Breast Cancer

The use of cannabinoids as anticancer agents.

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“It is well-established that cannabinoids exert palliative effects on some cancer-associated symptoms. In addition evidences obtained during the last fifteen years support that these compounds can reduce tumour growth in animal models of cancer.

Cannabinoids have been shown to activate an ER-stress related pathway that leads to the stimulation of autophagy-mediated cancer cell death.

In addition, cannabinoids inhibit tumour angiogenesis and decrease cancer cell migration.

The mechanisms of resistance to cannabinoid anticancer action as well as the possible strategies to develop cannabinoid-based combinational therapies to fight cancer have also started to be explored.

In this review we will summarize these observations (that have already helped to set the bases for the development of the first clinical studies to investigate the potential clinical benefit of using cannabinoids in anticancer therapies) and will discuss the possible future avenues of research in this area.” http://www.ncbi.nlm.nih.gov/pubmed/26071989

“… cannabinoids have been shown to alleviate nausea and vomit induced by chemotherapy and several cannabinoid-based medicines [Marinol (THC) and Cesamet (nabilone, a synthetic analogue of THC)] are approved for this purpose. Cannabinoids also inhibit pain, and Sativex (a standardized cannabis extract) has been approved in Canada for the treatment of cancer-associated pain. Other potential palliative effects of cannabinoids in oncology include appetite stimulation and attenuation of wasting. In addition to these palliative actions of cannabinoids in cancer patients, THC and other cannabinoids exhibit antitumour effects in animal models of cancer… a large body of scientific evidences strongly support THC and other cannabinoid agonists exert anticancer actions in preclinical models of cancer… In conclusion there exist solid scientific evidences supporting that cannabinoids exhibit a remarkable anticancer activity in preclinical models of cancer. Since these agents also show an acceptable safety profile, clinical studies aimed at testing them as single agents or in combinational therapies are urgently needed.” http://www.sciencedirect.com/science/article/pii/S0278584615001190

The Antitumor Activity of Plant-Derived Non-Psychoactive Cannabinoids.

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“As a therapeutic agent, most people are familiar with the palliative effects of the primary psychoactive constituent of Cannabis sativa (CS), Δ9-tetrahydrocannabinol (THC), a molecule active at both the cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptor subtypes.

Through the activation primarily of CB1 receptors in the central nervous system, THC can reduce nausea, emesis and pain in cancer patients undergoing chemotherapy.

During the last decade, however, several studies have now shown that CB1 and CB2 receptor agonists can act as direct antitumor agents in a variety of aggressive cancers.

In addition to THC, there are many other cannabinoids found in CS, and a majority produces little to no psychoactivity due to the inability to activate cannabinoid receptors.

For example, the second most abundant cannabinoid in CS is the non-psychoactive cannabidiol (CBD). Using animal models, CBD has been shown to inhibit the progression of many types of cancer including glioblastoma (GBM), breast, lung, prostate and colon cancer.

This review will center on mechanisms by which CBD, and other plant-derived cannabinoids inefficient at activating cannabinoid receptors, inhibit tumor cell viability, invasion, metastasis, angiogenesis, and the stem-like potential of cancer cells.

We will also discuss the ability of non-psychoactive cannabinoids to induce autophagy and apoptotic-mediated cancer cell death, and enhance the activity of first-line agents commonly used in cancer treatment.”

Role of Cannabinoid Receptor CB2 in HER2 Pro-oncogenic Signaling in Breast Cancer.

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“Pharmacological activation of cannabinoid receptors elicits antitumoral responses in different cancer models. However, the biological role of these receptors in tumor physio-pathology is still unknown…

Our findings reveal an unprecedented role of CB2 as a pivotal regulator of HER2 pro-oncogenic signaling in breast cancer, and they suggest that CB2 may be a biomarker with prognostic value in these tumors.”

A selective, non-toxic CB2 cannabinoid o-quinone with in vivo activity against triple negative breast cancer.

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“Triple-negative breast cancer (TNBC) represents a subtype of breast cancer characterized by high aggressiveness. There is no current targeted therapy for these patients whose prognosis, as a group, is very poor.

Here, we report the synthesis and evaluation of a potent antitumor agent in vivo for this type of breast cancer designed as a combination of quinone/cannabinoid pharmacophores.

This new compound (10) has been selected from a series of chromenopyrazolediones with full selectivity for the non-psychotropic CB2 cannabinoid receptor and with efficacy in inducing death of human TNBC cell lines.

The dual concept quinone/cannabinoid was supported by the fact that compound 10 exerts antitumor effect by inducing cell apoptosis through activation of CB2 receptors and through oxidative stress.

Notably, it did not show either cytotoxicity on non-cancerous human mammary epithelial cells nor toxic effects in vivo suggesting that it may be a new therapeutic tool for the management of TNBC.”

http://www.ncbi.nlm.nih.gov/pubmed/25671648

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

Modulation of the tumor microenvironment and inhibition of EGF/EGFR pathway: Novel anti-tumor mechanisms of Cannabidiol in breast cancer.

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“The anti-tumor role and mechanisms of Cannabidiol (CBD), a non-psychotropic cannabinoid compound, are not well studied especially in triple-negative breast cancer (TNBC).

In the present study, we analyzed CBD’s anti-tumorigenic activity against highly aggressive breast cancer cell lines including TNBC subtype.

We show here -for the first time-that CBD significantly inhibits epidermal growth factor (EGF)-induced proliferation and chemotaxis of breast cancer cells.

Further studies revealed that CBD inhibits EGF-induced activation of EGFR, ERK, AKT and NF-kB signaling pathways as well as MMP2 and MMP9 secretion.

In addition, we demonstrated that CBD inhibits tumor growth and metastasis in different mouse model systems.

Analysis of molecular mechanisms revealed that CBD significantly inhibits the recruitment of tumor-associated macrophages in primary tumor stroma and secondary lung metastases…

In summary, our study shows -for the first time-that CBD inhibits breast cancer growth and metastasis through novel mechanisms by inhibiting EGF/EGFR signaling and modulating the tumor microenvironment.

These results also indicate that CBD can be used as a novel therapeutic option to inhibit growth and metastasis of highly aggressive breast cancer subtypes including TNBC, which currently have limited therapeutic options and are associated with poor prognosis and low survival rates.”

http://www.ncbi.nlm.nih.gov/pubmed/25660577

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

Antiestrogenic effects of marijuana smoke condensate and cannabinoid compounds.

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“The antiestrogenic effects of marijuana smoke condensate (MSC) and three major cannabinoids, ie., delta9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN), were evaluated…

The results showed that MSC induced the antiestrogenic effect via the ER-mediated pathway, while THC, CBD, and CBN did not have any antiestrogenic activity.

This suggests that the combined effects of the marijuana smoke components are responsible for the antiestrogenicity of marijuana use.”

http://www.ncbi.nlm.nih.gov/pubmed/16392670

“Antiestrogen treatment of breast cancer: an overview.”  http://www.ncbi.nlm.nih.gov/pubmed/7044524

“Newly Found Estrogen Pathway Suggests Novel Breast Cancer Targets”   http://www.genengnews.com/gen-news-highlights/newly-found-estrogen-pathway-suggests-novel-breast-cancer-targets/81250405/

“New Estrogen Mechanism Holds Novel Cancer Treatment Promise”
http://www.counselheal.com/articles/11565/20140929/new-estrogen-mechanism-holds-novel-cancer-treatment-promise.htm

“CB1 and CB2 receptors are novel molecular targets for Tamoxifen and 4OH-Tamoxifen.”  http://www.ncbi.nlm.nih.gov/pubmed/24148245

“Scientists discover new role estrogen plays in cancer growth”  http://www.nydailynews.com/life-style/health/scientists-discover-new-role-estrogen-plays-cancer-growth-article-1.1957877

“Antiestrogen-induced remissions in stage IV breast cancer.”  http://www.ncbi.nlm.nih.gov/pubmed/1021225

“Antiestrogenic effects of marijuana smoke condensate and cannabinoid compounds.”  http://www.ncbi.nlm.nih.gov/pubmed/16392670

“New estrogen-related breast cancer mechanism detected”   http://www.medicalnewstoday.com/articles/283168.php

“Δ(9)-tetrahydrocannabinol targeting estrogen receptor signaling: the possible mechanism of action… 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).”  http://www.ncbi.nlm.nih.gov/pubmed/25177025

“Anti-Estrogen Drugs to Treat Breast Cancer”  http://www.fccc.edu/cancer/types/breast/treatment/hormonal/anti-estrogen.html

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

 

Cannabis oil stopped my cancer says Lake Macquarie’s Susannah Patch

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“A LAKE Macquarie woman whose ‘‘aggressive’’ breast cancer spread to various parts of her body including her spine and lungs credits her remarkable recovery to cannabis oil.

Awaba woman Susannah Patch, 44, is one of a growing number of Hunter people who have treated themselves using an underground network of cannabis oil suppliers.

Although she had surgery, radiotherapy and chemotherapy, Ms Patch says most of her improvement has come since stopping chemotherapy against the advice of the cancer specialists and continuing with cannabis oil…

‘It is a distinct possibility that the cannabinoids may have ‘‘a place in the future treatment of cancer,’’

http://www.theherald.com.au/story/2587931/cannabis-oil-stopped-my-cancer/?cs=12

“It’s breast cancer awareness month. Please, BE AWARE:” http://www.thctotalhealthcare.com/its-breast-cancer-awareness-month-please-be-aware/

“A laboratory study of cannabidiol in estrogen receptor positive and estrogen receptor negative breast cancer cells showed that it caused cancer cell death while having little effect on normal breast cells.” http://www.cancer.gov/cancertopics/pdq/cam/cannabis/patient/page2

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

“Cannabidiol, a safe and non-psychotropic ingredient of the marijuana plant Cannabis sativa,” http://www.ncbi.nlm.nih.gov/pubmed/19690824

“Cannabidiol (CBD) Shown To Kill Breast Cancer Cells” http://www.cafemom.com/group/99198/forums/read/19190923/Cannabidiol_CBD_Shown_To_Kill_Breast_Cancer_Cells

“Here, we show that Δ9-tetrahydrocannabinol (THC), reduces human breast cancer cell proliferation by blocking the progression of the cell cycle and by inducing apoptosis.” http://www.ncbi.nlm.nih.gov/pubmed/16818634

“Programmed Cell Death (Apoptosis)” http://www.ncbi.nlm.nih.gov/books/NBK26873/

“Cannabis has been shown to kill cancer cells…”
http://www.cancer.gov/cancertopics/pdq/cam/cannabis/patient/page1

“…cannabinoids may be able to kill cancer cells while protecting normal cells… A laboratory study of delta-9-THC… showed that it damaged or killed the cancer cells… A laboratory study of cannabidiol… showed that it caused cancer cell death…” http://www.cancer.gov/cancertopics/pdq/cam/cannabis/patient/page2

“Cannabinoids appear to kill tumor cells but do not effect their nontransformed counterparts and may even protect them from cell death.” http://www.cancer.gov/cancertopics/pdq/cam/cannabis/healthprofessional/page4

“Cannabis oil stopped my cancer says Lake Macquarie’s Susannah Patch” http://www.theherald.com.au/story/2587931/cannabis-oil-stopped-my-cancer/?cs=12

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

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

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“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.

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“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.

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“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