Anti-proliferative and anti-angiogenic effects of CB2R agonist (JWH-133) in non-small lung cancer cells (A549) and human umbilical vein endothelial cells: an in vitro investigation.
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Category Archives: Lung Cancer
Cannabinoid Receptors, CB1 and CB2, as Novel Targets for Inhibition of Non-Small Cell Lung Cancer Growth and Metastasis
“Cannabinoid receptors are expressed in human lung cancers”
“Recently, CB1 and CB2 have been shown to be overexpressed on tumor cells compared to normal cells in various types of cancers, such as breast and liver, and therefore could be used as novel targets for cancer. In addition, several cannabinoids, including THC and cannabidiol, synthetic cannabinoid-agonists JWH-133, Win55,212-2, were shown to inhibit tumor growth and progression of several types of cancers, including glioma, glioblastoma multiforme, breast, prostate, colon carcinomas, leukemia and lymphoid tumors.”
“There are three general types of cannabinoids: phytocannabinoids, THC and cannabidiol, are derived from plants; endogenous cannabinoids, 2AG and AEA, which are produced inside the body; and synthetic cannabinoids, JWH-133/JWH-015, CP-55 and Win55,212-2.”
“Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide; however, only limited therapeutic treatments are available. Hence, we investigated the role of cannabinoid receptors, CB1 and CB2, as novel therapeutic targets against NSCLC…”
“These results suggest that CB1 and CB2 could be used as novel therapeutic targets against NSCLC.”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3025486/
Inhibition of cancer cell invasion by cannabinoids via increased expression of tissue inhibitor of matrix metalloproteinases-1.
“Cannabinoids, in addition to having palliative benefits in cancer therapy, have been associated with anticarcinogenic effects. Although the antiproliferative activities of cannabinoids have been intensively investigated, little is known about their effects on tumor invasion.”
“Increased expression of TIMP-1 mediates an anti-invasive effect of cannabinoids. Cannabinoids may therefore offer a therapeutic option in the treatment of highly invasive cancers.”
“There is considerable evidence to suggest an important role for cannabinoids in conferring anticarcinogenic activities. In this study, we identified TIMP-1 as a mediator of the anti-invasive actions of MA, a hydrolysis-stable analog of the endocannabinoid anandamide, and THC, a plant-derived cannabinoid.”
“In conclusion, our results suggest that there exists a signaling pathway by which the binding of cannabinoids to specific receptors leads via intracellular MAPK activation to induction of TIMP-1 expression and subsequent inhibition of tumor cell invasion. To our knowledge, this is the first report of TIMP-1–dependent anti-invasive effects of cannabinoids.”
Inhibitory effects of cannabinoid CB1 receptor stimulation on tumor growth and metastatic spreading: actions on signals involved in angiogenesis and metastasis.
“Stimulation of cannabinoid CB1 receptors… inhibits the growth of a rat thyroid cancer cell-derived tumor… also blocks the growth of tumors… the hypothesis that CB1 receptor stimulation interferes not only with angiogenesis but also with metastatic processes was tested in a widely used model of metastatic infiltration in vivo, the Lewis lung carcinoma… Our findings indicate that CB1 receptor agonists might be used therapeutically to retard tumor growth in vivo by inhibiting at once tumor growth, angiogenesis, and metastasis.”
Cannabinoid receptor agonists are mitochondrial inhibitors: a unified hypothesis of how cannabinoids modulate mitochondrial function and induce cell death.
“Time-lapse microscopy of human lung cancer (H460) cells showed that the endogenous cannabinoid anandamide (AEA), the phyto-cannabinoid Delta-9-tetrahydrocannabinol (THC) and a synthetic cannabinoid HU 210 all caused morphological changes characteristic of apoptosis… These data demonstrate that AEA, THC, and HU 210 are all able to cause changes in integrated mitochondrial function, directly, in the absence of cannabinoid receptors.”
Media Ignored Expert’s Shocking Findings That Marijuana Helps Prevent Lung Cancer: Now It’s Med-School Material
“You’d think it would have been very big news in the spring of 2005 when Donald Tashkin, a professor of pulmonology at UCLA’s David Geffin School of Medicine, revealed at a conference that components of marijuana smoke, although they damage cells in respiratory tissue, somehow prevent them from becoming malignant. But headlines announcing “Pot Doesn’t Cause Cancer” did not ensue. ”
“As to the highly promising implication of his own study — that something in marijuana stops damaged cells from becoming malignant — Tashkin noted that an anti-proliferative effect of THC has been observed in cell-culture systems and animal models of brain, breast, prostate, and lung cancer. THC has been shown to promote known apoptosis (damaged cells die instead of reproducing) and to counter angiogenesis (the process by which blood vessels are formed — a requirement of tumor growth). Other antioxidants in cannabis may also be involved in countering malignancy, Tashkin said.”
Pot Smoking Not Linked to Lung Cancer – WebMD
“People who smoke marijuana do not appear to be at increased risk for developing lung cancer, new research suggests.
While a clear increase in cancer risk was seen among cigarette smokers in the study, no such association was seen for regular cannabis users.
Even very heavy, long-term marijuana users who had smoked more than 22,000 joints over a lifetime seemed to have no greater risk than infrequent marijuana users or nonusers.
The findings surprised the study’s researchers, who expected to see an increase in cancer among people who smoked marijuana regularly in their youth.”
Read more: http://www.webmd.com/lung-cancer/news/20060523/pot-smoking-not-linked-to-lung-cancer
Marijuana Does Not Raise Lung Cancer Risk -FoxNews
“People who smoke marijuana do not appear to be at increased risk for developing lung cancer, new research suggests.
While a clear increase in cancer risk was seen among cigarette smokers in the study, no such association was seen for regular cannabis users.
Even very heavy, long-term marijuana users who had smoked more than 22,000 joints over a lifetime seemed to have no greater risk than infrequent marijuana users or nonusers.
The findings surprised the study’s researchers, who expected to see an increase in cancer among people who smoked marijuana regularly in their youth.”
Read more: http://www.foxnews.com/story/0,2933,196678,00.html
Anti-emetic efficacy and toxicity of nabilone, a synthetic cannabinoid, in lung cancer chemotherapy.
Abstract
“Nabilone, a synthetic cannabinoid, and Prochlorperazine were compared in a double-blind crossover study of 34 patients with lung cancer undergoing a 3-day schedule of chemotherapy with Cyclophosphamide, Adriamycin and Etoposide. Symptom scores were significantly better for patients on nabilone for nausea, retching and vomiting (P less than 0.05). Fewer subjects vomited with nabilone (P = 0.05) and the number of vomiting episodes was lower (P less than 0.05); no patients on nabilone required additional parenteral anti-emetic. More patients preferred nabilone for anti-emetic control (P less than 0.005). Adverse effects common with nabilone were drowsiness (57%), postural dizziness (35%) and lightheadedness (18%). Euphoria was seen in 14% and a “high” in 7%. Erect systolic blood pressure was lower in nabilone patients on Day 1 (P = 0.05) but postural hypotension was a major problem in only 7%. Nabilone is an effective oral anti-emetic drug for moderately toxic chemotherapy, but the range and unpredictability of its side-effects warrant caution in its use.”
Mechanism of action of cannabinoids: how it may lead to treatment of cachexia, emesis, and pain.
“Many patients with life-threatening diseases such as cancer experience severe symptoms that compromise their health status and deny them quality of life. Patients with cancer often experience cachexia, pain, and depression,which translate into an unacceptable quality of life. The discovery of the endocannabinoid system has led to a renewed interest in the use of cannabinoids for the management of nausea, vomiting, and weight loss arising either from cancer or the agents used to treat cancer. The endocannabinoid system has been found to be a key modulator of systems involved in pain perception, emesis, and reward pathways. As such, it represents a target for development of new medications for controlling the symptoms associated with cancer. Although the cannabinoid receptor agonist tetrahydrocannabinol and one of its analogs are currently the only agents approved for clinical use, efforts are under way to devise other strategies for activating the endocannabinoid system for therapeutic uses.”