Certain marijuana components may suppress the tumors of highly invasive cancers, a new study finds. In laboratory tests, cannabinoids, the active components in marijuana, were found to slow the spread of lung and cervical cancer tumors, according to researchers Robert Ramer and Burkhard Hinz of the University of Rostock in Germany.
Proponents of medical marijuana believe that cannabinoids reduce the side effects of cancer treatment, such as pain, weight loss and vomiting.
The study, published in the Jan. 2 issue of the Journal of the National Cancer Institute, finds that the compounds may also have an anticancer effect; however, more research is needed to determine whether the laboratory results will hold true in humans, the authors wrote.
In addition to suppressing tumor cell invasion, cannabinoids also stimulated the expression of TIMP-1, an inhibitor of a group of enzymes involved in tumor cell invasion. “To our knowledge, this is the first report of TIMP-1-dependent anti-invasive effects of cannabinoids,” the authors wrote. “This signaling pathway may play an important role in the antimetastatic action of cannabinoids, whose potential therapeutic benefit in the treatment of highly invasive cancers should be addressed in clinical trials.”
– Article from FOX News
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Inhibition of Cancer Cell Invasion by Cannabinoids via Increased Expression of Tissue Inhibitor of Matrix Metalloproteinases-1
Journal of the National Cancer Institute
December 25, 2007
Oxford University Press
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.
Matrigel-coated and uncoated Boyden chambers were used to quantify invasiveness and migration, respectively, of human cervical cancer (HeLa) cells that had been treated with cannabinoids (the stable anandamide analog R( )-methanandamide [MA] and the phytocannabinoid 9-tetrahydrocannabinol [THC]) in the presence or absence of antagonists of the CB1 or CB2 cannabinoid receptors or of transient receptor potential vanilloid 1 (TRPV1) or inhibitors of p38 or p42/44 mitogen?activated protein kinase (MAPK) pathways. Reverse transcriptase?polymerase chain reaction (RT-PCR) and immunoblotting were used to assess the influence of cannabinoids on the expression of matrix metalloproteinases (MMPs) and endogenous tissue inhibitors of MMPs (TIMPs). The role of TIMP-1 in the anti-invasive action of cannabinoids was analyzed by transfecting HeLa, human cervical carcinoma (C33A), or human lung carcinoma cells (A549) cells with siRNA targeting TIMP-1. All statistical tests were two-sided.
Without modifying migration, MA and THC caused a time- and concentration-dependent suppression of HeLa cell invasion through Matrigel that was accompanied by increased expression of TIMP-1. At the lowest concentrations tested, MA (0.1 ?M) and THC (0.01 ?M) led to a decrease in invasion (normalized to that observed with vehicle-treated cells) of 61.5% (95% CI = 38.7% to 84.3%, P < .001) and 68.1% (95% CI = 31.5% to 104.8%, P = .0039), respectively. The stimulation of TIMP-1 expression and suppression of cell invasion were reversed by pretreatment of cells with antagonists to CB1 or CB2 receptors, with inhibitors of MAPKs, or, in the case of MA, with an antagonist to TRPV1. Knockdown of cannabinoid-induced TIMP-1 expression by siRNA led to a reversal of the cannabinoid-elicited decrease in tumor cell invasiveness in HeLa, A549, and C33A cells. Conclusion
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.
CONTEXT AND CAVEATS
Treatment with cannabinoids had been shown to reduce the invasiveness of cancer cells, but the cellular mechanisms underlying this effect were unclear.
Cancer cells treated with combinations of cannabinoids, antagonists of cannabinoid receptors, and siRNA to tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) were assessed for invasiveness, protein expression, and activation of signal transduction pathways.
The expression of TIMP-1 was shown to be stimulated by cannabinoid receptor activation and to mediate the anti-invasive effect of cannabinoids.
Clarification of the mechanism of cannabinoid action may help investigators to explore their therapeutic benefit.
The relevance of the findings to the behavior of tumor cells in vivo remains to be determined.
– Authors: Robert Ramer, Burkhard Hinz
– Affiliation of authors: Institute of Toxicology and Pharmacology, University of Rostock, Rostock, Germany
– Correspondence to: Burkhard Hinz, PhD, Institute of Toxicology and Pharmacology, University of Rostock, Schillingallee 70, Rostock D-18057, Germany (e-mail: [email protected]).