Monday, January 26, 2015

Proapoptotic effect of endocannabinoids in prostate cancer cells

http://www.spandidos-publications.com/10.3892/or.2015.3746

  • Authors:
    • O. Orellana-Serradell
    • C. E. Poblete
    • C. Sanchez
    • E. A. Castellón
    • I. Gallegos
    • C. Huidobro
    • M. N. Llanos
    • H. R. Contreras
  • Corresponding author:
  • View Affiliations
  • Published online on: Wednesday, January 21, 2015
  • DOI: 10.3892/or.2015.3746

Abstract

In the early stages, prostate cancer is androgen‑ dependent; therefore, medical castration has shown significant results during the initial stages of this pathology. Despite this early effect, advanced prostate cancer is resilient to such treatment. Recent evidence shows that derivatives of Cannabis sativa and its analogs may exert a protective effect against different types of oncologic pathologies. The purpose of the present study was to detect the presence of cannabinoid receptors (CB1 and CB2) on cancer cells with a prostatic origin and to evaluate the effect of the in vitro use of synthetic analogs. In order to do this, we used a commercial cell line and primary cultures derived from prostate cancer and benign prostatic hyperplasia. The presence of the CB1 and CB2 receptors was determined by immunohistochemistry where we showed a higher expression of these receptors in later stages of the disease (samples with a high Gleason score). Later, treatments were conducted using anandamide, 2-arachidonoyl glycerol and a synthetic analog of anandamide, methanandamide. Using the MTT assay, we proved that the treatments produced a cell growth inhibitory effect on all the different prostate cancer cultures. This effect was demonstrated to be dose-dependent. The use of a specific CB1 receptor blocker (SR141716) confirmed that this effect was produced primarily from the activation of the CB1 receptor. In order to understand the MTT assay results, we determined cell cycle distribution by flow cytometry, which showed no variation at the different cell cycle stages in all the cultures after treatment. Treatment with endocannabinoids resulted in an increase in the percentage of apoptotic cells as determined by Annexin V assays and caused an increase in the levels of activated caspase-3 and a reduction in the levels of Bcl-2 confirming that the reduction in cell viability noted in the MTT assay was caused by the activation of the apoptotic pathway. Finally, we observed that endocannabinoid treatment activated the Erk pathway and at the same time, produced a decrease in the activation levels of the Akt pathway. Based on these results, we suggest that endocannabinoids may be a beneficial option for the treatment of prostate cancer that has become nonresponsive to common therapies.
 

Friday, January 23, 2015

German Scientists Have Confirmed an Amazing Link between Cannabis and Cancer Suppression

Researchers at the Institute of Toxicology and Pharmacology of Rostock University in Germany further confirm the profound benefits of Cannabis

 

R
esearchers at the Institute of Toxicology and Pharmacology of Rostock University in Germany rang in the New Year with excellent news for the world. In a study, Prof. Burkhard Hinz and his scientists put the active ingredients in cannabis up to the claims of holding an ability to truly kill cancer cells, even going further into the chemistry to find out exactly how this medical miracle takes place.  

Hinz’s repertoire with cannabis goes back a ways. In 2008 his research team was the first to discover that active ingredients actually slowed the migration of tumor cells into the surrounding tissues, this migration is what commonly leads metastasis, which is when cancer moves out from one affected area and into the rest of the body.   
The research has been published in the January 2015 edition of the journal Biochemical Pharmacology with the title “New Insights into Antimetastic and Antiangiogenic Effects of Cannabinoids.” What they found was that both tetrahydrocannabinol (THC or known as Delta-9-Tetrahydrocannabinol) and cannabidiolalso an active substance and originating from cannabiscontribute to the destruction of tumor cells by stimulating the formation of a specific proteinICAM-1. By acting on the surface of the cells attacked by cancer, the proteins link themselves to the immune system’s own defensive cellsmaking the cancerous cells burst. The active ingredients, thus, prevent cancerous cells from forming blood vessels which allow the cancer to take root and grow.

This is, of course, very encouraging news, but the professor gave no timeline with respect to when his studies will progress onward with the process of producing an actual medicine. Hinz emphasized that the study is still at an early stage, and said, “We are far from putting our discoveries into practice on a clinical level. However, our results are further evidence that cannabinoids mediate a series of potentially therapeutic uses.” 

 

http://www.sciencedirect.com/science/article/pii/S1937644814000082

Chapter Two – New Insights into Antimetastatic and Antiangiogenic Effects of Cannabinoids



Abstract

Cannabinoids exert antitumorigenic effects via multiple mechanisms. Of these, antimetastatic and antiangiogenic actions have attracted considerable interest in the past years. Regarding the underlying antimetastatic mechanism, several studies revealed cannabinoids to alter the gene expression of cancer cells toward a less-aggressive phenotype and to modulate their secretomic profile. Cannabinoids likewise modulate the release of factors from tumor cells that subsequently suppress the chemoattraction of vessel cells thereby conferring antiangiogenesis. Among the diverse mediators of cannabinoids' antitumorigenic action, the tissue inhibitor of matrix metalloproteinases-1, which is released from cancer cells upon cannabinoid treatment, has been implicated as a pivotal factor conferring both anti-invasive properties of cancer cells as well as antiangiogenic capacities of endothelial cells. In addition, cannabinoids have been shown to inhibit angiogenic capacities of endothelial cells directly via suppressing their proliferation, tube formation, and migration. This chapter reviews the cell- and substance-specific antitumorigenic mechanisms of cannabinoids with particular consideration of their antimetastatic/anti-invasive and antiangiogenic actions. In addition, beneficial interactions of cannabinoids with currently used chemotherapeutics as well as the influence of cannabinoids on tumor-immune surveillance are addressed. Collectively, the currently available data suggest cannabinoids as a potential tool in modern cancer pharmacotherapy.

Keywords

  • Angiogenesis;
  • Cancer;
  • Cannabinoids;
  • Metastasis;
  • Tumor cell invasion

Corresponding author: E-mail: burkhard.hinz@med.uni-rostock.de

Sunday, January 18, 2015

Study Shows THC May Limit Damage Caused By Heart Attack

http://www.medicaljane.com/2013/07/22/thc-is-beneficial-for-brain-heart-health/

Small Amounts Of THC Defend Against Heart Attacks

A recent study conducted by the Felsenstein Medical Research Center in Israel offered some new evidence of the medical value of Cannabis. The study, published in the Journal of Biochemical Pharmacology, was conducted to determine what effect small amounts of tetrahydrocannabinol (THC) has on heart protection. In order to do so, they conducted an experiment using mice as the subjects.
“A single ultra low dose of THC before ischemia [Insufficient Blood flow] is a safe and effective treatment that reduces myocardial ischemic [Heart Attack] damage.” – Felsenstein Medical Research Center, Israel
Researchers administered small amounts of THC (4 times less than the intoxicating amount) to mice before simulating a heart attack by restricting their blood flow.
The THC was administered on three different schedules in reference to the “heart attack”: 2 hours prior, 48 hours prior, and 3 weeks prior of continuous treatment.
In order to gauge the effect of THC in this study, researchers observed a number of common signs and/or residual effects of heart attacks. In each schedule of THC administration the study reported an improvement in each of the categories.

THC Has The Upper Hand On Cardiac Damage

Fractional Shortening is a ratio used to objectively rate the level of efficiency that a ventricle is working with. In observing this ratio, researchers found that THC treatment resulted in a 4.7% increase.
Troponin T is a regulatory protein found in cardiac muscle that leaks into the bloodstream in the case of cardiovascular damage. High volumes of it in the blood is often used to diagnose heart attacks. Researchers found that THC treatment reduced the amount of Troponin T by an average of 4 nano grams per milliliter.
The area of dead tissue caused by insufficient blood flow decreased by 6% after THC treatment.
In cases where blood is unable to reach a specific area, an infarction can form. This is an area in which the tissue dies, due to a process called necrosis. The researchers measured the size of these infarctions and found they decreased 6% after THC treatment.
Better heart health undoubtedly results in a longer lifespan. The study above suggests an ultra-low dose of THC can be beneficial in preparation for cardiac surgery. It could limit the damage incurred by the patient and possibly aid in the recovery.

Tuesday, December 2, 2014

Marijuana fights Alzheimer’s disease, new study indicates

http://blog.sfgate.com/smellthetruth/2014/11/29/marijuana-fights-alzheimers-disease-study-indicates/


Another study is adding evidence to the case for the treatment and prevention of Alzheimer’s disease with the compounds in cannabis.
Research published in the Journal of Alzheimer’s Disease this September “strongly suggest that THC [the main active ingredient in marijuana] could be a potential therapeutic treatment option for Alzheimer’s disease through multiple functions and pathways.”
More than five million Americans have Alzheimer’s today. One in three seniors will die with Alzheimer’s or another dementia, and Alzheimer’s is the sixth leading cause of death in the nation, costing America about $203 billion in 2013.
Chuanhai Cao and other researchers at the University of South Florida and Thomas Jefferson University wanted to investigate the “potential therapeutic qualities of Δ9-tetrahydrocannabinol (THC) with respect to slowing or halting the hallmark characteristics of Alzheimer’s disease.”
So they treated Alzheimer’s research cells (N2a-variant amyloid-β protein precursor (AβPP) cells) with THC and examined them for amyloid-β at the 6, 24, and 48-hour time markers. Amyloid-β is a type of protein that is linked to Alzheimer’s symptoms. The researchers found THC “to be effective at lowering Aβ levels … in a dose-dependent manner.”
The main active ingredient in pot “directly interacts” with amyloid-β, “thereby inhibiting aggression”. THC was also effective at lowering other key Alzheimer’s Disease markers. Furthermore “no toxicity” was observed from the THC. The researchers also found THC “enhances” the function of the cell’s energy factories — the mitochondria.
“THC is known to be a potent antioxidant with neuroprotective properties, but this is the first report that the compound directly affects Alzheimer’s pathology by decreasing amyloid beta levels, inhibiting its aggregation, and enhancing mitochondrial function,” stated study lead author Chuanhai Cao, PhD and a neuroscientist at the Byrd Alzheimer’s Institute and the USF College of Pharmacy.
“Decreased levels of amyloid beta means less aggregation, which may protect against the progression of Alzheimer’s disease. Since THC is a natural and relatively safe amyloid inhibitor, THC or its analogs may help us develop an effective treatment in the future.”
Other research in the same journal that month indicates THC boosts the body’s natural anti-Alzheimer’s fighting mechanism — the endocannabinoid system.
Alzheimer’s Disease is thought to result from a lifetime of brain inflammation. Cannabis is one of the most safe anti-inflammatories in medicine. Some neuroscientists believe a bout of pot smoking in early adulthood may prevent Alzheimer’s onset later in life. Cannabis slows brain aging, Time reported in 2012.
Smoking, vaping, or eating the pot molecules THC and CBD directly effects nerve cell function, reducing chronic brain inflammation, oxidative stress, and cellular dysfunction — all the while promoting stability of the human body’s internal environment (homeostasis) and healthy brain cells (neurotrophic support), studies show.
“What we found was that not only did the single puff a day reverse the memory impairment but also restarted neurogenesis,” Ohio State University, Gary Wenk told the Seattle Post Intelligencer this year.
Other studies have shown THC inhibits other key pathological markers of Alzheimer’s Disease.
The U.S. government has patented marijuana molecule CBD as a neuroprotectant, evan as it maintains that cannabis is a schedule 1 drug with no medical use and high potential for abuse. The federal drug war is blocking deeper research into cannabis’ impacts on brain disease, Wenk states.

Wednesday, November 19, 2014

Cannabis ‘Dramatically Reduces’ Growth of Brain Cancer Cells: New Study

http://naturalsociety.com/cannabis-dramatically-reduces-growth-brain-cancer-cells-new-study/ 

http://mct.aacrjournals.org/content/early/2014/11/12/1535-7163.MCT-14-0402.abstract

The Combination of Cannabidiol and Δ9-Tetrahydrocannabinol Enhances the Anticancer Effects of Radiation in an Orthotopic Murine Glioma Model

  1. Wai M. Liu*
+ Author Affiliations
  1. Department of Oncology, Division of Clinical Sciences, St George's, University of London, London, United Kingdom.
  1. *Corresponding Author:
    Wai Liu, Department of Oncology, Division of Clinical Sciences, St George's, University of London, Second Floor, Jenner Wing, London, SW17 0RE, United Kingdom. Phone: 44-20-8725-5037; Fax: 44-20-8725-0158; E-mail: w.liu@sgul.ac.uk

Abstract

High-grade glioma is one of the most aggressive cancers in adult humans and long-term survival rates are very low as standard treatments for glioma remain largely unsuccessful. Cannabinoids have been shown to specifically inhibit glioma growth as well as neutralize oncogenic processes such as angiogenesis. In an attempt to improve treatment outcome, we have investigated the effect of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) both alone and in combination with radiotherapy in a number of glioma cell lines (T98G, U87MG, and GL261). Cannabinoids were used in two forms, pure (P) and as a botanical drug substance (BDS). Results demonstrated a duration- and dose-dependent reduction in cell viability with each cannabinoid and suggested that THC-BDS was more efficacious than THC-P, whereas, conversely, CBD-P was more efficacious than CBD-BDS. Median effect analysis revealed all combinations to be hyperadditive [T98G 48-hour combination index (CI) at FU50, 0.77–1.09]. Similarly, pretreating cells with THC-P and CBD-P together for 4 hours before irradiation increased their radiosensitivity when compared with pretreating with either of the cannabinoids individually. The increase in radiosensitivity was associated with an increase in markers of autophagy and apoptosis. These in vitro results were recapitulated in an orthotopic murine model for glioma, which showed dramatic reductions in tumor volumes when both cannabinoids were used with irradiation (day 21: 5.5 ± 2.2 mm3 vs. 48.7 ± 24.9 mm3 in the control group; P < 0.01). Taken together, our data highlight the possibility that these cannabinoids can prime glioma cells to respond better to ionizing radiation, and suggest a potential clinical benefit for glioma patients by using these two treatment modalities. Mol Cancer Ther; 1–13. ©2014 AACR.
  • Received May 12, 2014.
  • Revision received September 8, 2014.
  • Accepted September 23, 2014.

Tuesday, September 16, 2014

Clinical endocannabinoid deficiency (CECD) revisited: Can this concept explain the therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions?

http://www.ncbi.nlm.nih.gov/pubmed/24977967

Neuro Endocrinol Lett. 2014 Jun 30;35(3):198-201. [Epub ahead of print]

Abstract

OBJECTIVES:

Ethan B. Russo's paper of December 1, 2003 explored the concept of a clinical endocannabinoid deficiency (CECD) underlying the pathophysiology of migraine, fibromyalgia, irritable bowel syndrome and other functional conditions alleviated by clinical cannabis.

METHODS:

Available literature was reviewed, including searches via the National Library of medicine database and other sources.

RESULTS:

A review of the literature indicates that significant progress has been made since Dr. Ethan B. Russo's landmark paper, just ten years ago (February 2, 2004). Investigation at that time suggested that cannabinoids can block spinal, peripheral and gastrointestional mechanisms that promote pain in headache, fibromyalgia, irritable bowel syndrome and muscle spasm.

CONCLUSION:

Subsequent research has confirmed that underlying endocannabinoid deficiencies indeed play a role in migraine, fibromyalgia, irritable bowel syndrome and a growing list of other medical conditions. Clinical experience is bearing this out. Further research and especially, clinical trials will further demonstrate the usefulness of medical cannabis. As legal barriers fall and scientific bias fades this will become more apparent.
PMID:
24977967
[PubMed - as supplied by publisher]

Thursday, September 11, 2014

CANNABINOIDS INCREASE LUNG CANCER CELL LYSIS (cell breakdown) BY LYMPHOKINE-ACTIVATED KILLER CELLS VIA UPREGULATION OF ICAM-1

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

Biochem Pharmacol. 2014 Jul 25. pii: S0006-2952(14)00420-1. doi: 10.1016/j.bcp.2014.07.014. [Epub ahead of print]

Abstract

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. Using lung cancer cell lines (A549, H460) and metastatic cells derived from a lung cancer patient, the present study addressed the impact of cannabinoid-induced ICAM-1 on cancer cell adhesion to lymphokine-activated killer (LAK) cells and LAK cell-mediated cytotoxicity. 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. Increased cancer cell lysis by CBD was likewise abrogated when CBD-induced ICAM-1 expression was blocked by specific siRNA or by antagonists to cannabinoid receptors (CB1, CB2) and to transient receptor potential vanilloid 1. In addition, enhanced killing of CBD-treated cancer cells was reversed by preincubation of LAK cells with an antibody to lymphocyte function associated antigen-1 (LFA-1) suggesting intercellular ICAM-1/LFA-1 crosslink as crucial event within this process. ICAM-1-dependent pro-killing effects were further confirmed for the phytocannabinoid Δ9-tetrahydrocannabinol (THC) and R(+)-methanandamide, a stable endocannabinoid analogue. Finally, each cannabinoid elicited no significant increase of LAK cell-mediated lysis of non-tumor bronchial epithelial cells, BEAS-2B, associated with a far less pronounced (CBD, THC) or absent (R(+)-methanandamide) ICAM-1 induction as compared to cancer cells. 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.
Copyright © 2014. Published by Elsevier Inc.


Lysis

From Wikipedia, the free encyclopedia
This article is about the biological definition of the word Lysis. For other uses, see Lysis (disambiguation).
Lysis (/ˈlsɪs/; Greek λύσις lýsis, "a loosing" from λύειν lýein, "to unbind") refers to the breaking down of a cell, often by viral, enzymic, or osmotic mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a "lysate".