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.”
Antiangiogenic activity of the endocannabinoid anandamide: correlation to its tumor-suppressor efficacy.
“Endocannabinoids are now emerging as suppressors of key cell-signaling pathways involved in cancer cell growth, invasion, and metastasis. We have previously observed that the metabolically stable anandamide analog, 2-methyl-2′-F-anandamide (Met-F-AEA) can inhibit the growth of thyroid cancer in vivo. Our hypothesis was that the anti-tumor effect observed could be at least in part ascribed to inhibition of neo-angiogenesis… our results suggest that anandamide could be involved in the control of cancer growth targeting both tumor cell proliferation and the angiogenic stimulation of the vasculature.”
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 Smokers Breathe Easy Says The University of Alabama
“As of January 10, 2012, a new study has been published in the Journal of the American Medical Association exonerating marijuana from the bad reputation of being as harmful to your lungs when smoked as tobacco cigarettes. Researchers at the University of California San Francisco and the University of Alabama at Birmingham completed a twenty-year study between 1986 and 2006 on over 5,000 adults over the age of 21 in four American cities. Study co-author Dr. Stefan Kertesz is a professor of preventive medicine at the University of Alabama at Birmingham. He explained that the studies measured the pulmonary obstruction in individuals with up to seven joint-years of lifetime exposure (one joint per day for seven years or one joint per week for 49 years). “What this study clarifies,” Kertesz explains in a released video, “is that the relationship to marijuana and lung function changes depending on how much a person has taken in over the course of a lifetime.”
“…findings suggest that occasional use of marijuana may not be linked with unfavorable consequences on pulmonary function. Marijuana is designated by the U.S. government as a Schedule I drug, which declares it has no medicinal purposes. Previous studies have shown that the drug can be used to treat multiple sclerosis, glaucoma, nausea, and pain. It has been known to have beneficial effects on pain control, mood, appetite, and managing of other chronic symptoms. Despite these facts, marijuana continues to be depicted as more damaging to us than it’s legal counterpart tobacco. Marijuana activists, medical patients, and recreational users alike will rejoice knowing the evidence shows otherwise.”
Read more: http://nugs.com/article/marijuana-smokers-breathe-easy-says-the-university-of-alabama.html
Study: Smoking Marijuana Not Linked with Lung Damage – TIME
“Marijuana does not impair lung function—at least not in the doses inhaled by the majority of users, according to the largest and longest study ever to consider the issue, which was published today in the Journal of the American Medical Association.
Researchers working on a long-term study of risk factors for cardiovascular disease (the Coronary Artery Risk Development in Young Adults or CARDIA study) tested the lung function of 5115 young adults over the course of 20 years, starting in 1985 when they were aged 18 to 30.
The study was “well conducted” and is “essentially confirmatory of the findings from several previous studies that have examined the association between marijuana smoking and lung function,” says Dr. Donald Tashkin, professor of medicine at UCLA and a leading scientist in the area. He was not associated with the new research.
“The major strengths of this study are that it included a far larger number of subjects followed for longer than any of these previous studies,” he adds.”
Read more: http://healthland.time.com/2012/01/10/study-smoking-marijuana-not-linked-with-lung-damage/