Cannabinoids and Melanoma
The following is a review of Glodde et al’s 2015 paper, and Armstrong et al’s 2015 papers on cannabinoids and melanoma cells. Prepared by Jacklyn G.
Tetrahydrocannabinol, also known as THC, may have an effect on melanoma cells. In a recent study, Differential role of cannabinoids in the pathogenesis of skin cancer (Glodde et.al), it was found that cannabinoids can slow down the growth of cancer cells. The study focused on two parts: the growth of different melanoma cells in vitro and in vivo and the effects of the endogenous cannabinoid system on cancer cells. In a different study, Exploiting Cannabinoid-Induced Cytitixic Autophagy to Drive Melanoma Cell Death (Armstrong et.al), it was proven that THC can cause a rapid increase in cell death without harming melanocytes in human cells. These studies prove that THC may be a viable candidate for treating melanoma.
The first study mentioned decided to evaluate if the endogenous cannabinoid system had an effect on skin tumors. The study evaluated: fibrosarcomas, papillomas, and melanomas on mice. Endogenous cannabinoids showed almost no effect on the tumor type fibrosarcomas. They also had no effect on the growth or amount of papillomas and melanomas in the mice. Overall, the study concluded that the endogenous cannaboid system did not influence skin tumors. While the endogenous cannabinoid system had no effect on melanoma, exogenous cannabinoids like cannabinoid cannabidiol (CBD) did have an effect on tumors.
The first study mentioned, explored the growth of cancer cells in vitro. There were three different tested effects on the mice: 5μM of THC,10μM of THC, and a control group. The mice were injected with melanoma cells into their dermis on their dorsal side. Then the mice were given THC periodically. The study concluded that THC did not inhibit the growth of tumors in vitro. The tumors grew exponentially. When 5 and 10μM were added to the mice, the tumors grew at roughly the exact same rate as the mice used as control over a 72-hour period. Since the mice all grew tumors at the same rate regardless of the injected THC, it was inferred that THC does not have an effect on cancer cells in vitro. While this study disproves the effects of THC in vitro, other studies differ in their conclusions.
In the second study mentioned, the viability of cancer cells in vitro was also tested. Accept, this study tested the viability of cells when THC and CBD is added to the cancer cells versus simply adding THC like the first study. When THC and CBD were used together, they reduced the viability of cancer cells. When 2.5 μM of THC and CBD was used on A375, SK-MEL-28, and CHL-1 cancer cells the cell viability lowered, approaching zero in vitro. This study proves that THC could be a viable candidate used to lower the amount of cancer cells in vitro if CBD was also added.
The first study mentioned did prove that THC inhibits growth of HCmel12 melanoma in CB1 and CB2 receptors in vivo. Over a period of twenty-five days, the tumors in the mice who were injected with THC grew significantly slower. Mice injected with the THC had tumors that were approximately 250mm^3, while the control mice produced tumors that were approximately 500mm^3 at the end of the twenty-five days. Since the mice injected with THC grew tumors roughly half the size. This intrigues the question: would THC have the same effect on HCmel12 melanoma in humans? Although, tumor growth suppression was not the only effect THC had on the injected mice.
The THC in the study also decreased inflammation in the tumor of HCmel12 melanoma. Mice injected with THC produced less than half of the percent of CD45+ immune cells. This would cause less inflammation in the microenvironment of the HCmel12 tumor. The study also proved that the density of blood vessels stayed the same in mice with added THC and the control mice.
The second study focused heavily on the self-elimination of human cancer cells. The study tested the visibility of autophagy in cancer cells CHL-1 and A375. THC doubled the amount of autophagy activity in CHL-1 and A375 cancer cells. This means that THC potentially doubles the amount of cell death in these specific cancer cells. If cancer cells are realizing their own mutations and eliminating themselves through autophagy, this would cause the death of cancer cells. The greater activity of autophagy, the more cancer cells that will be eliminated. The next goal would be to only eliminate cancer cells and avoid healthy melanocytes.
The second study mentioned also tested the viability of cancer cells versus melanocytes when THC was added to human cancer cells. The viability of CHL-1 and A375 cancer cells had approximately half of the viability of melanocytes when 6 μM of THC was added. When more than 6 μM of THC was given, the viability of melanocytes began to decrease. So, the dose of THC does effect melanocyte viability, but it has little effect before 6 μM. This means that THC has little effect on melanocytes compared to skin cancer cells. This is positive because the goal is to simply target the abnormally mutated cancer cells and leave the normal melanocytes alone.
At the end of the first study it was proven that THC, exogenous cannabinoids, can stop the growth of specific cancerous cells on the skin. THC does this in two parts. It slows down the growth of cancer cells and alters the tumors progression by effecting “neo-angiogenesis, cell migration and the immune system”. THC also works on “programmed cell death”. Even though this study was done on mice and not humans, the study’s conclusions indirectly suggest that it is possible for THC to slow the progression of human melanoma cancer cells. The second study added on to the first, proving that THC+CBD had an effect on the viability of tumors, while THC alone had far less of an impact on cancer cells. It explored the heavy impact THC had on autophagy, causing cell death. The study also emphasized the importance of THC safely killing mutated cancerous skin cells and having little effect on healthy skin cells. Overall, both of these studies contributed to the overarching hypothesis that THC and cannabinoids have an effect on cancer cells. Both studies proved that THC can reduce the growth and amount of cancer cells. This is an important discovery for human medicine. Melanoma kills thousands of people every year; if THC can reverse the effects of different types of melanoma, it could potentially save thousands of lives.
References:
- Glodde, N., et al. “Differential Role of Cannabinoids in the Pathogenesis of Skin Cancer.” LIFE SCIENCES, vol. 138, 2015, pp. 35-40, doi:10.1016/j.lfs.2015.04.003.
- Armstrong, JL, et al. “Exploiting Cannabinoid-Induced Cytotoxic Autophagy to Drive Melanoma Cell Death.” JOURNAL OF INVESTIGATIVE DERMATOLOGY, vol. 135, no. 6, 2015, pp. 1629-1637, doi:10.1038/jid.2015.45.