By Lindsay Christensen
The incidence and mortality of melanoma, an aggressive form of skin cancer, has increased substantially over the last thirty years. It is the leading cause of death out of all the types of skin cancer, and it has a very high potential for metastasis. According to the “Cancer Facts and Figures 2016 Report” published by The American Cancer Society, it is estimated that 76,380 people total in the United States will be diagnosed with melanoma in 2016, and 10,130 people will die from this disease (“Cancer Facts and Figures,” 2016). If melanoma is caught early on, it can often be removed through surgery. However, the five-year survival rates of the later stages of melanoma are extremely poor; these survival rates are 45% and 10% for those diagnosed with stage III and IV melanoma, respectively.
Immunotherapy and drugs for melanoma have demonstrated limited potential, as melanomas are quite resistant to conventional treatment. For all of these reasons, novel treatment approaches are desperately needed for addressing melanoma. A substance called quercetin may offer a much-needed alternative treatment approach.
A review article published in Frontiers in Nutrition on October 31, 2016, has brought new hope to the horizon for the treatment of melanoma. The article, titled “Quercetin as an Emerging Anti-Melanoma Agent: A Four-Focus Area Therapeutic Development Strategy,” suggests that quercetin, a bioflavonoid found in many fruits and vegetables, may be a bona-fide anti-melanoma compound (Harris, Donovan, Branco, Limes, Burd, 2016).
Based on research done on lines of melanoma cells, the researchers found that quercetin plays four distinct roles in the human body that affect the development of melanoma. I have outlined these four roles below:
Role 1: Quercetin has the ability to “modulate cellular bioreduction potential and associated signaling cascades.” In simpler terms, this means that quercetin has the ability to scavenge free radicals in the body, which are atoms or groups of atoms that have unpaired electrons, which makes the atoms unstable. These unstable atoms try to “steal” electrons from other molecules within the body, which damages the molecules. The molecules that have had their electrons “stolen” then try to steal electrons from other molecule, leading to a free radical cascade, or a “domino effect.” Quercetin brings this cascade to a halt by donating electrons to the molecules that have been “robbed.” This lends stability to the molecules and allows them to function properly. Therefore, this prevents further oxidative damage to the body, including damage to DNA. Damage to DNA can lead to the development of cancerous cells, including melanoma, so sources of antioxidants are crucial in the prevention of cancer.
Interestingly, while low concentrations of quercetin offer antioxidant effects, high concentrations of quercetin exert pro-oxidant effects; these pro-oxidant effects may be beneficial in that their effect is anticarcinogenic, meaning it inhibits the development of cancer. High concentrations of quercetin may lead to oxidation of quercetin into substances called o-quinones. O-quinones have been shown to promote the death (apoptosis) of cancer cells. O-quinones are closely linked to tyrosinase, an enzyme that is a key player in melanoma due to its role in creating melanin and other skin pigments in melanocytes. Tyrosinase reacts with quercetin to make o-quinones, which then exert their cancer-cell-killing effects on melanoma cells (Harris, Donovan, Branco, Limes, Burd, 2016).
Role 2: The second important role of quercetin in melanoma is that it promotes normal transcription, the first step in gene expression, of the p53 gene, otherwise known as the tumor suppressor gene. The tumor suppressor gene functions as its name suggests: it protects normal cells from morphing into cancerous cells and forming tumors. Abnormalities in the p53 tumor suppressor gene are the number one common molecular abnormality seen in human cancer (Bray, Schorl, Hall, 1998). In melanoma cells, the administration of quercetin led to a significant increase in the expression of p53, and thus increased the number of cancerous cells in a state of cell death (Harris, Donovan, Branco, Limes, Burd, 2016). Quercetin administration may lead to an increase in the transcription of p53 tumor suppressor gene by stimulating a substance called nuclear factor E2-related factor (Nrf2). Nrf2 helps to regulate gene expression, ensuring that p53 is produced correctly and carries out its crucial activities within the body.
Role 3: Quercetin beneficially regulates epigenetic changes in the body. Epigenetics refers to changes in organisms that occur due to modification of gene expression, rather than of the genetic code. Epigenetic changes due to environmental factors have been correlated with the development of cancer, so substances that can manage epigenetic changes in a beneficial way could be very valuable in the treatment of cancer. Methylation of several types of tumor suppressor genes has been shown to increase melanoma. Methylation is the process by which chemical groups called methyl groups are added or removed from DNA, affecting its expression. Quercetin has demonstrated an ability to inhibit methylation of certain tumor suppressor genes. Quercetin’s ability to inhibit and demethylate these genes may help in both the prevention and treatment of melanoma.
Role 4: Finally, quercetin may be useful in the development of combination therapies for melanoma, because it has the ability to enhance current conventional treatments. Quercetin’s antioxidant (in small doses) and pro-oxidant (in large doses) properties, along with its abilities to affect cell signaling cascades, gene transcription, and promotion of cancer cell death, may make it a very useful treatment to combine with other therapies for melanoma. Quercetin may enhance the activities of certain pharmaceutical drugs that are already in use for melanoma treatment. Furthermore, advances in the bioavailability of quercetin, such as combining it with liposomes to enhance its delivery through cell membranes, may make it even more potent.
Quercetin has the potential to be an excellent therapeutic modality in the treatment of melanoma. Through its ability to affect cell bioreduction and signaling cascades, promote normal gene transcription, manage epigenetic changes, and enhance currently available therapies, quercetin may be the key to unlocking more effective treatment for melanoma.
1. Bray, S.E., Schorl, C., Hall, P.A. (1998). The challenge of p53: Linking biochemistry, biology, and patient management. Stem Cells, 16(4), 248-260. Retrieved from http://onlinelibrary.wiley.com/doi/10.1002/stem.160248/abstract.
2. Cancer Facts & Figures. (2016). American Cancer Society. Retrieved from http://www.cancer.org/acs/groups/content/@research/documents/document/acspc-047079.pdf.
3. Harris, Z., Donovan, M.G., Branco, G.M., Limes, K.H., and Burd, R. (2016). Quercetin as an Emerging Anti-Melanoma Agent: A Four-Focus Area Therapeutic Development Strategy. Frontiers in Nutrition. http://dx.doi.org/10.3389/fnut.2016.00048.
About the author: Lindsay has her Bachelors of Science in Biomedical Science, with an Emphasis in Nutrition, from National University of Health Sciences. When she is not studying nutrition or researching and writing, Lindsay enjoys working out, rock climbing, hiking, skiing, and having adventures outdoors. She is also quite passionate about her camera and taking nature photography. You can read more about Lindsay’s Lyme disease experience, as well read all her latest thoughts and research on health, by visiting her website and blog, Rock On Nutrition, at https://rockonnutrition.me/.