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Cannabinoids Can Cause Cell Death in Endometrial Cancer

Endometrial cancer is one of the most commonly diagnosed cancers in the United States. It’s estimated that just over 61,000 new cases were diagnosed in 2017, accounting for 3.6% of all cancer diagnoses for the year, and resulting in over 10,000 deaths. This female-specific cancer affects the lining of the uterine wall, and exists in two different forms. Type I, which accounts for 80-90% of all endometrial cancers, is dependent on the hormone estrogen. Type II is estrogen-independent, and is typically more aggressive in nature. The five-year survival rate is quite high for endometrial cancer, but it isn’t 100%, so research is ongoing to understand this cancer and develop new treatments. A paper recently published in the Journal of Physiology and Biochemistry shows how cannabinoids may fill this role.

One way our cells communicate with each other is using chemical signals. The cell sending a signal releases a chemical into the space between cells. Neighboring cells with the proper receptors receive the signal, and respond accordingly. This is a common mechanism of cell-cell communication, and is used to control a number of important biological processes, like controlling the fate of stem cells, or inducing a process of programmed cell death. Cannabinoids, like THC and CBD, act as chemical signals when ingested or inhaled. Neurons that have the right receptors are activated by these signals, giving them their range of biological effects.

Our bodies produce two chemicals called AEA and 2-AG, which are collectively termed endocannabinoids (ECs), so named for their structural similarity to THC and CBD. These chemicals interact with two receptors, CB1 and CB2. These receptors regulate several cellular responses, including programmed cell death. Further, it has been shown that some types of cancer express the CB receptors, making them potentially sensitive to EC signals. In this paper, the authors investigate the ability of ECs, THC, and CBD to induce cell death in endometrial cancer cells.

THE STUDY

Researchers often use human cells grown in culture for the study of cancer. In this case, the authors used two endometrial cancer cell lines, representing Type I and Type II cancers. They also used a non-cancerous cell line as a control. Cells were treated with each of the four cannabinoids, and the effect was assessed using two complementary methods. Both tests showed that the ECs and CBD were able to kill the cancerous cells, but had no effect on the non-cancerous cells. THC had no effect on any of the cell lines, even at the highest concentrations. This demonstrates the ability of certain cannabinoids to kill endometrial cancer cells.

Next, the authors chose to determine whether or not these cells were undergoing programmed cell death. This is a well-studied process, and has many telltale signs. The authors chose to look at multiple related and complementary signals. AEA and CBD treatments generated evidence of programmed cell death in Type I cells. No such evidence was found for Type II cells, regardless of treatment. These tests indicate that AEA and CBD can induce programmed cell death in Type I, but not Type II, endometrial cancer cells.

Finally, they tested which receptors were important for this process. In addition to CB1 and CB2, there is a third receptor called TRPVI that is activated by the ECs. In these tests, they deactivated each of the receptors individually, then treated the cells with cannabinoids. If the cannabinoid was unable to kill the cells, then that receptor is necessary for cell death. For the Type I cells, only the third receptor was required for cell death, while none of them were necessary for Type II cell death. In practical terms, this means that TRPVI, and not the CB receptors, are targets for cancer therapy.

CONCLUSIONS

Several interesting results can be pulled from this paper. For one thing, it shows that CBD may be an effective treatment for both Type I and Type II endometrial cancers. CBD induced programmed cell death in Type I cells only, but it was actually more effective for killing Type II cells. Type II is the more aggressive cancer, so this is good news for Type II patients. Second, it identifies TRPVI as a potential drug target. While this is useful in itself, it also demonstrates the broader applications of cannabis-based research.

As always, the results must be met with skepticism and caution. The concentrations of cannabinoids used in these tests are quite high; it may not be safe to administer the amounts necessary to reach these concentrations. Further, cells growing in a dish are very different from cancer cells in the body. They generate their own signals that cause them to grow out of control, which may counteract the effects of cannabinoids. Also, individual genetic differences may influence how any particular patient will respond to medication. Nevertheless, these results point to CBD and other cannabinoids as a potential treatment for this common type of cancer.

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