Category Archives: Cancer

Spontaneous Cannabinoid Receptor 2 (CB2) Expression in the Cochlea of Adult Albino Rat and Its Up-Regulation after Cisplatin Treatment

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“We provide evidence for the presence of cannabinoid CB2 receptors in some cellular types of the cochlea of the adult albino rat. Cannabinoids and their receptors are increasingly being studied because of their high potential for clinical use. As a hyperspecialized portion of the peripheral nervous system, study of the expression and function of cannabinoid receptors in the hearing organ is of high interest. Stria vascularis and inner hair cells express CB2 receptor, as well as neurites and cell bodies of the spiral ganglion. Cellular types such as supporting cells and outer hair cells, in which the expression of other types of functional receptors has been reported, do not significantly express CB2 receptors in this study. An up-regulation of CB2 gene expression was detected after an ototoxic event such as cisplatin treatment, probably due to pro-inflammatory events triggered by the drug. That fact suggests promising potential of CB2receptor as a therapeutic target for new treatments to palliate cisplatin-induced hearing loss and other ototoxic events which triggers inflammatory pathways.”  http://www.ncbi.nlm.nih.gov/pubmed/27564061

“In conclusion, evidence for the presence of cannabinoid CB2 receptor by immunohystochemistry and by RT-qPCR was provided. An immunolabeling of CB2 antibodies in four structures of the adult rat cochlea was found. That was, stria vascularis, inner hair cells, auditory afferent nerves and cell bodies of the spiral ganglion. Up-regulation of CB2 gene expression in animals exposed to CDDP treatment was also detected, when compared with healthy animals. This fact was partially supported by the higher immunofluorescence observed in the stria vascularis of CDDP-treated animals if compared with the healthy ones. These results suggest a considerable promising potential of CB2 receptor as a target of new treatments against CDDP-induced ototoxicity, and probably against other inflammatory diseases in the inner ear. Further research is needed to determine the functionality of CB2receptors in the organ of Corti and the potential therapeutic role of agonists and antagonists of these receptors.”  http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0161954

“Study: Cannabinoids a Potential Treatment Option for Chemotherapy-Induced Hearing Loss” http://www.theweedblog.com/study-cannabinoids-potential-treatment-option-chemotherapy-induced-hearing-loss/

Cannabidiol rather than Cannabis sativa extracts inhibit cell growth and induce apoptosis in cervical cancer cells.

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“Cervical cancer remains a global health related issue among females of Sub-Saharan Africa, with over half a million new cases reported each year.

Different therapeutic regimens have been suggested in various regions of Africa, however, over a quarter of a million women die of cervical cancer, annually. This makes it the most lethal cancer amongst black women and calls for urgent therapeutic strategies.

In this study we compare the anti-proliferative effects of crude extract of Cannabis sativa and its main compound cannabidiol on different cervical cancer cell lines.

Results obtained indicate that both cannabidiol and Cannabis sativa extracts were able to halt cell proliferation in all cell lines at varying concentrations.

They further revealed that apoptosis was induced by cannabidiol as shown by increased subG0/G1 and apoptosis through annexin V. Apoptosis was confirmed by overexpression of p53, caspase 3 and bax. Apoptosis induction was further confirmed by morphological changes, an increase in Caspase 3/7 and a decrease in the ATP levels.

CONCLUSIONS:

In conclusion, these data suggest that cannabidiol rather than Cannabis sativa crude extracts prevent cell growth and induce cell death in cervical cancer cell lines.”

http://www.ncbi.nlm.nih.gov/pubmed/27586579

“Different ethnic groups around the world use Cannabis sativa for smoking, preparing concoctions to treat diseases, and for various cultural purposes. It has been found to be effective against a variety of disorders including neurodegerative disorders, autoimmune diseases, and cancer. Cannabis sativa in particular cannabidiol, we propose it plays important role in helping the body fight cancer through inhibition of pain and cell growth.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5009497/

Cancer is a Preventable Disease that Requires Major Lifestyle Changes

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“This year, more than 1 million Americans and more than 10 million people worldwide are expected to be diagnosed with cancer, a disease commonly believed to be preventable.

Only 5–10% of all cancer cases can be attributed to genetic defects, whereas the remaining 90–95% have their roots in the environment and lifestyle. The lifestyle factors include cigarette smoking, diet (fried foods, red meat), alcohol, sun exposure, environmental pollutants, infections, stress, obesity, and physical inactivity.

The evidence indicates that of all cancer-related deaths, almost 25–30% are due to tobacco, as many as 30–35% are linked to diet, about 15–20% are due to infections, and the remaining percentage are due to other factors like radiation, stress, physical activity, environmental pollutants etc.

Therefore, cancer prevention requires smoking cessation, increased ingestion of fruits and vegetables, moderate use of alcohol, caloric restriction, exercise, avoidance of direct exposure to sunlight, minimal meat consumption, use of whole grains, use of vaccinations, and regular check-ups.

In this review, we present evidence that inflammation is the link between the agents/factors that cause cancer and the agents that prevent it. In addition, we provide evidence that cancer is a preventable disease that requires major lifestyle changes.

In summary, this review outlines the preventability of cancer based on the major risk factors for cancer. The percentage of cancer-related deaths attributable to diet and tobacco is as high as 60–70% worldwide.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2515569/

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

 

Cannabinoids As Potential Treatment for Chemotherapy-Induced Nausea and Vomiting.

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“Despite the advent of classic anti-emetics, chemotherapy-induced nausea is still problematic, with vomiting being somewhat better managed in the clinic.

If post-treatment nausea and vomiting are not properly controlled, anticipatory nausea-a conditioned response to the contextual cues associated with illness-inducing chemotherapy-can develop. Once it develops, anticipatory nausea is refractive to current anti-emetics, highlighting the need for alternative treatment options.

One of the first documented medicinal uses of Δ(9)-tetrahydrocannabinol (Δ(9)-THC) was for the treatment of chemotherapy-induced nausea and vomiting (CINV), and recent evidence is accumulating to suggest a role for the endocannabinoid system in modulating CINV.

Here, we review studies assessing the therapeutic potential of cannabinoids and manipulations of the endocannabinoid system in human patients and pre-clinical animal models of nausea and vomiting.”

http://www.ncbi.nlm.nih.gov/pubmed/27507945

Inhibition of interleukin-8 release in the human colonic epithelial cell line HT-29 by cannabinoids.

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“We have investigated the effects of cannabinoid agonists and antagonists on tumour necrosis factor-alpha (TNF-alpha)-induced secretion of interleukin-8 from the colonic epithelial cell line, HT-29.

The cannabinoid receptor agonists [(-)-3-[2-hydroxy-4-(1,1-dimethyl-heptyl)-phenyl]4-[3-hydroxypropyl]cyclo-hexan-1-ol] (CP55,940); Delta-9-tetrahydrocannabinol; [R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl) methyl] pyrrolo[1,2,3-de]1,4-benzoxazin-6-yl](1-naphthyl) methanone mesylate] (WIN55,212-2) and 1-propyl-2-methyl-3-naphthoyl-indole (JWH 015) inhibited TNF-alpha induced release of interleukin-8 in a concentration-dependent manner.

We conclude that in HT-29 cells, TNF-alpha-induced interleukin-8 release is inhibited by cannabinoids through activation of cannabinoid CB(2) receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/12498928

“Essential involvement of interleukin-8 (IL-8) in acute inflammation.”  http://www.ncbi.nlm.nih.gov/pubmed/7964163

“Interleukin-8 (IL-8) is known to possess tumorigenic and proangiogenic properties. Overexpression of IL-8 has been detected in many human tumors, including colorectal cancer (CRC). IL-8 promotes tumor growth, metastasis, chemoresistance and angiogenesis, implying IL-8 to be an important therapeutic target in CRC.”  http://www.ncbi.nlm.nih.gov/pubmed/20648559

Modulation of L-α-lysophosphatidylinositol/GPR55 mitogen-activated protein kinase (MAPK) signaling by cannabinoids.

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“This study has implications for developing new therapeutics for the treatment of cancer, pain, and metabolic disorders.

GPR55 is activated by l-α-lysophosphatidylinositol (LPI) but also by certain cannabinoids.

In this study, we investigated the GPR55 pharmacology of various cannabinoids, including analogues of the CB1 receptor antagonist Rimonabant®, CB2 receptor agonists, and Cannabis sativa constituents.

Here, we show that CB1 receptor antagonists can act both as agonists alone and as inhibitors of LPI signaling under the same assay conditions. This study clarifies the controversy surrounding the GPR55-mediated actions of SR141716A; some reports indicate the compound to be an agonist and some report antagonism. In contrast, we report that the CB2 ligand GW405833 behaves as a partial agonist of GPR55 alone and enhances LPI signaling. GPR55 has been implicated in pain transmission, and thus our results suggest that this receptor may be responsible for some of the antinociceptive actions of certain CB2 receptor ligands.

Here, we report that the little investigated cannabis constituents CBDV, CBGA, and CBGV are potent inhibitors of LPI-induced GPR55 signaling.

The phytocannabinoids Δ9-tetrahydrocannabivarin, cannabidivarin, and cannabigerovarin are also potent inhibitors of LPI.

Our findings also suggest that GPR55 may be a new pharmacological target for the following C. sativa constituents: Δ9-THCV, CBDV, CBGA, and CBGV.

These Cannabis sativa constituents may represent novel therapeutics targeting GPR55.”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249141/

“Lysophosphatidylinositol (LPI) is a bioactive lipid generated by phospholipase A2 which is believed to play an important role in several diseases.”  http://www.ncbi.nlm.nih.gov/pubmed/22285325

 “The putative cannabinoid receptor GPR55 promotes cancer cell proliferation.  In this issue of Oncogene, two groups demonstrated that GPR55 is expressed in various cancer types in an aggressiveness-related manner, suggesting a novel cancer biomarker and a potential therapeutic target.” http://www.ncbi.nlm.nih.gov/pubmed/21057532
“The orphan G protein-coupled receptor GPR55 promotes cancer cell proliferation via ERK. These findings reveal the importance of GPR55 in human cancer, and suggest that it could constitute a new biomarker and therapeutic target in oncology.” http://www.ncbi.nlm.nih.gov/pubmed/20818416
“The putative cannabinoid receptor GPR55 defines a novel autocrine loop in cancer cell proliferation. These findings may have important implications for LPI as a novel cancer biomarker and for its receptor GPR55 as a potential therapeutic target.”  http://www.ncbi.nlm.nih.gov/pubmed/20838378
“L-α-lysophosphatidylinositol meets GPR55: a deadly relationship. Evidence points to a role of L-α-lysophosphatidylinositol (LPI) in cancer.”  http://www.ncbi.nlm.nih.gov/pubmed/21367464

Endocannabinoid system as a regulator of tumor cell malignancy – biological pathways and clinical significance.

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“The endocannabinoid system (ECS) comprises cannabinoid receptors (CBs), endogenous cannabinoids, and enzymes responsible for their synthesis, transport, and degradation of (endo)cannabinoids.

To date, two CBs, CB1 and CB2, have been characterized; however, orphan G-protein-coupled receptor GPR55 has been suggested to be the third putative CB.

Several different types of cancer present abnormal expression of CBs, as well as other components of ECS, and this has been shown to correlate with the clinical outcome.

Although most effects of (endo)cannabinoids are mediated through stimulation of classical CBs, they also interact with several molecules, either prosurvival or proapoptotic molecules.

It should be noted that the mode of action of exogenous cannabinoids differs significantly from that of endocannabinoid and results from the studies on their activity both in vivo and in vitro could not be easily compared.

This review highlights the main signaling pathways involved in the antitumor activity of cannabinoids and the influence of their activation on cancer cell biology.

We also discuss changes in the expression pattern of the ECS in various cancer types that have an impact on disease progression and patient survival.

A growing amount of experimental data imply possible exploitation of cannabinoids in cancer therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/27486335

Preparation and characterization of Δ(9)-tetrahydrocannabinol-loaded biodegradable polymeric microparticles and their antitumoral efficacy on cancer cell lines.

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“Cannabinoids present an interesting therapeutic potential as antiemetics, appetite stimulants in debilitating diseases (cancer, AIDS and multiple sclerosis), analgesics, and in the treatment of multiple sclerosis and cancer, among other conditions.

However, despite their high clinical potential, only few dosage forms are available to date.

In this paper, the development of Δ(9)-tetrahydrocannabinol (THC) biodegradable microspheres as an alternative delivery system for cannabinoid parenteral administration is proposed.

As THC has shown therapeutic potential as anticancer drug, the efficacy of the microspheres was tested on different cancer cell lines.

Interestingly, the microspheres were able to inhibit cancer cell proliferation during the nine-day study period.

All the above results suggest that the use of biodegradable microspheres would be a suitable alternative delivery system for THC administration.”

http://www.ncbi.nlm.nih.gov/pubmed/23773072

In vitro and in vivo evaluation of Δ⁹-tetrahidrocannabinol/PLGA nanoparticles for cancer chemotherapy.

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“Nanoplatforms can optimize the efficacy and safety of chemotherapy, and thus cancer therapy. However, new approaches are encouraged in developing new nanomedicines against malignant cells.

In this work, a reproducible methodology is described to prepare Δ(9)-tetrahidrocannabinol (Δ(9)-THC)-loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles against lung cancer.

Cell viability studies comparing the activity of the nanoformulations against human A-549 and murine LL2 lung adenocarcinoma cells, and human embryo lung fibroblastic MRC-5 cells revealed a statistically significant selective cytotoxic effect toward the lung cancer cell lines.

In addition, cytotoxicity assays in A-549 cells demonstrated the more intense anticancer activity of Δ(9)-THC-loaded PEGylated PLGA nanoparticles.

These promising results were confirmed by in vivo studies in LL2 lung tumor-bearing immunocompetent C57BL/6 mice.”

http://www.ncbi.nlm.nih.gov/pubmed/25899283

Endocannabinoid system as a regulator of tumor cell malignancy – biological pathways and clinical significance

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“The endocannabinoid system (ECS) comprises cannabinoid receptors (CBs), endogenous cannabinoids, and enzymes responsible for their synthesis, transport, and degradation of (endo)cannabinoids.

To date, two CBs, CB1 and CB2, have been characterized; however, orphan G-protein-coupled receptor GPR55 has been suggested to be the third putative CB.

Several different types of cancer present abnormal expression of CBs, as well as other components of ECS, and this has been shown to correlate with the clinical outcome.

Although most effects of (endo)cannabinoids are mediated through stimulation of classical CBs, they also interact with several molecules, either prosurvival or proapoptotic molecules.

It should be noted that the mode of action of exogenous cannabinoids differs significantly from that of endocannabinoid and results from the studies on their activity both in vivo and in vitro could not be easily compared.

This review highlights the main signaling pathways involved in the antitumor activity of cannabinoids and the influence of their activation on cancer cell biology.

We also discuss changes in the expression pattern of the ECS in various cancer types that have an impact on disease progression and patient survival.

A growing amount of experimental data imply possible exploitation of cannabinoids in cancer therapy.”

https://www.dovepress.com/endocannabinoid-system-as-a-regulator-of-tumor-cell-malignancy-ndash-b-peer-reviewed-article-OTT