Dr. Weeks’ Comment: No news here. Known for years. Why does the government not allow its free use? Profits over people? Hmm…
“…Cumulatively, these studies indicate that THC has anti-tumorigenic and anti-metastatic effects against lung cancer. ..”
Experimental and Molecular Therapeutics
Δ-9 Tetrahydrocannabinol inhibits growth and metastasis of lung cancer.
Anju Preet, Ramesh Ganju and Jerome GroopmanDOI: Published May 2007
AACR Annual Meeting– Apr 14-18, 2007; Los Angeles, CA
Abstract
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Lung cancer is the major cause of cancer-related mortality worldwide. Many of these over-express epidermal growth factor receptor (EGFR), and are usually highly aggressive and resistant to chemotherapy. Recent studies have shown that Δ-9 Tetrahydrocannabinol (THC), the major component of Cannabis sativa, possess anti-tumor properties against various types of cancers. However, not much is known about its effect on lung cancer. In this study, we sought to characterize the effect of THC on EGF-induced growth and metastasis of human non small lung cancer cell (NSCLC) lines A549 and SW-1573. We demonstrate that these cell lines and primary tumor samples derived from lung cancer patients express cannabinoids receptors CB1 and CB2, the known targets for THC action. We further show that THC inhibits EGF-induced growth in these cell lines. In addition THC attenuated EGF-stimulated chemotaxis and chemoinvasion. Next we characterized the effect of THC on in vivo lung cancer growth and metastasis in a murine model. A549 cells were implanted in SCID mice (n=6 per group) through subcutaneous and intravenous injections to generate subcutaneous and lung metastatic cancer, respectively. THC (5mg/kg body wt.) was administered once daily through intraperitoneal injections for 21 days. The mice were analyzed for tumor growth and lung metastasis. A significant reduction (~50%) in tumor weight and volume were observed in THC treated animals compared to the vehicle treated animals. THC treated animals also showed a significant (~60%) reduction in macroscopic lesions on the lung surface in comparison to vehicle treated control. Immunohistochemical analysis of the tumor samples from THC treated animals revealed anti-proliferative and anti-angiogenic effects of THC with significant reduction in staining for Ki67, a proliferative marker and CD31, an endothelial marker indicative of vascularization. Investigation into the signaling events associated with reduced EGF-induced functional effects revealed that THC also inhibits EGF-induced Akt phosphorylation. Akt is a central signaling molecule of EGFR-mediated signaling pathways and it regulates a diverse array of cellular functions, including proliferation, angiogenesis, invasion and apoptosis. Cumulatively, these studies indicate that THC has anti-tumorigenic and anti-metastatic effects against lung cancer. Novel therapies against EGFR overexpressing, aggressive and chemotherapy resistant lung cancers may include targeting the cannabinoids receptors.
SUMMARY
Summary: The active ingredient in marijuana cuts tumor growth in common lung cancer in half and significantly reduces the ability of the cancer to spread, say researchers who tested the chemical in both lab and mouse studies.Share: FULL STORY
The active ingredient in marijuana cuts tumor growth in common lung cancer in half and significantly reduces the ability of the cancer to spread, say researchers at Harvard University who tested the chemical in both lab and mouse studies.
They say this is the first set of experiments to show that the compound, Delta-tetrahydrocannabinol (THC), inhibits EGF-induced growth and migration in epidermal growth factor receptor (EGFR) expressing non-small cell lung cancer cell lines. Lung cancers that over-express EGFR are usually highly aggressive and resistant to chemotherapy.
THC that targets cannabinoid receptors CB1 and CB2 is similar in function to endocannabinoids, which are cannabinoids that are naturally produced in the body and activate these receptors. The researchers suggest that THC or other designer agents that activate these receptors might be used in a targeted fashion to treat lung cancer.
“The beauty of this study is that we are showing that a substance of abuse, if used prudently, may offer a new road to therapy against lung cancer,” said Anju Preet, Ph.D., a researcher in the Division of Experimental Medicine.
Acting through cannabinoid receptors CB1 and CB2, endocannabinoids (as well as THC) are thought to play a role in variety of biological functions, including pain and anxiety control, and inflammation. Although a medical derivative of THC, known as Marinol, has been approved for use as an appetite stimulant for cancer patients, and a small number of U.S. states allow use of medical marijuana to treat the same side effect, few studies have shown that THC might have anti-tumor activity, Preet says. The only clinical trial testing THC as a treatment against cancer growth was a recently completed British pilot study in human glioblastoma.
In the present study, the researchers first demonstrated that two different lung cancer cell lines as well as patient lung tumor samples express CB1 and CB2, and that non-toxic doses of THC inhibited growth and spread in the cell lines. “When the cells are pretreated with THC, they have less EGFR stimulated invasion as measured by various in-vitro assays,” Preet said.
Then, for three weeks, researchers injected standard doses of THC into mice that had been implanted with human lung cancer cells, and found that tumors were reduced in size and weight by about 50 percent in treated animals compared to a control group. There was also about a 60 percent reduction in cancer lesions on the lungs in these mice as well as a significant reduction in protein markers associated with cancer progression, Preet says.
Although the researchers do not know why THC inhibits tumor growth, they say the substance could be activating molecules that arrest the cell cycle. They speculate that THC may also interfere with angiogenesis and vascularization, which promotes cancer growth.
Preet says much work is needed to clarify the pathway by which THC functions, and cautions that some animal studies have shown that THC can stimulate some cancers. “THC offers some promise, but we have a long way to go before we know what its potential is,” she said.
The research was presented at the 2007 meeting of the American Association for Cancer Research, held Apr 14-18, 2007 in Los Angeles, CA.
Story Source:
Materials provided by American Association for Cancer Research. Note: Content may be edited for style and length.
Journal Reference:
- Anju Preet, Ramesh Ganju and Jerome Groopman. Δ-9 Tetrahydrocannabinol inhibits growth and metastasis of lung cancer. Cancer Research: Experimental and Molecular Therapeutics, May 2007, Volume 67, Issue 9 Supplement [link]