There are many new discoveries through cancer research – and they are found from many new angles of looking at cancer. One of these angles is new pharmaceutical approaches that cause apoptosis, the death of the cancer cells. Other angles include nutritional approaches, antioxidant approaches, new surgical methods, and other methods that are outside the box and don’t fit in any of these categories.
Korean researchers at the Division of Molecular Cancer Research at the Soonchynhyang Medical Research Institute and the Soonchunhyung Environmental Health Center for Asbestos combined their efforts with other scientists to conduct cancer research and explore whether there was any new way to help those who have mesothelioma. Their mission was to check out the effects of a substance called quercetin on the body’s Nrf2 detoxification pathways for malignant mesothelioma cells.
What is Quercetin?
Quercetin is a natural plant pigment in the category of flavonoids that is found in fruits, vegetables, and grains. It acts as an antioxidant and can appreciably reduce inflammation, symptoms of allergies, and blood pressure. It has many influences on the immune system, such as:
• stabilizing mast cell function (these are the cells that are responsible for allergy symptoms)
• blocks the development of new cancerous growths, called angiogenesis
• scavenges and binds metals that affect lipid peroxidation and free radical production
• supports circulation by free radical scavenging
Quercetin consumption varies anywhere from 0 to 30 mg per day, depending on what foods are eaten in the daily diet. This important polyphenol is found in the following foods:
• red onions
• leafy vegetables
• black and green tea
• red wine
Red raspberries contain 3.58 mg per 100 grams (6 oz) portion size, so the amounts of quercetin taken in from food aren’t that high. Raspberries are one of the highest sources of the nutrient. Cancer research has found that if someone takes a 40 mg quercetin (isoquercitrin) supplement daily, this would be equivalent to consuming the quercetin content from 8-1/2 cups of fruits and vegetables.
What is the Nrf2 Pathway?
The body’s Nrf-2 pathway is one of the main detoxification pathways in the body. When activated, the Nrf-2 pathway turns on the genes that handle the free radicals in the body generated by toxins and is part of phase II detoxifying enzymes. It’s also involved in pathways for multidrug resistance. This pathway acts as the “captain” that says, “Release the crew that will take care of all the free radicals in the body from these toxins.” Some of these free radical genes are ones for glutathione reductases, TXN, and NADPH.
The Nrf-2 pathway is generally not activated until a toxin turns the genes on. Once turned on, cancer research suggests that the body can perform its detoxification processes.
Free radicals are created in the body by oxygen metabolism, chemotherapy agents, ionizing radiation, ultraviolet light, cytokines and low levels of oxygen. You need free radicals in the body for normal body functions but too many free radicals can damage cells and DNA. Cells have built-in defenses against these free radical insults such as antioxidant defense systems.
Previous cancer research has reported that increased oxidative stress and low levels of antioxidants are found in many types of cancer. Many anticancer drugs rely on free radical mechanisms to carry out their effects. These same scientists believe that it’s possible that cells with lowered antioxidant defenses can make the cells susceptible to chemo drugs. However, as the tumor progresses, cancer cells get more resistant to chemo drugs and develop into aggressive tumors. This happens frequently in those with mesothelioma.
The Nrf-2 pathway is of great importance in the prevention of cell dysfunction. Nrf-2 activation appears to be beneficial for cancer chemoprevention in early stages but as some cancers progress, the Nrf-2 pathway prevents the death of the cancer cells. The pathway is dysregulated in many types of cancers such as lung, gall bladder and head and neck cancers.
Cancer Research and the Nrf-2 Pathway
And that’s where the antioxidant quercetin fits into the picture.
The Nrf-2 pathway is a common molecular target for a variety of natural products that have anti-cancer properties. Quercetin has the unique ability to act as either an antioxidant or a pro-oxidant, depending on the situation at hand.
Higher doses of quercetin reduces the activities and levels of antioxidants in the cells, which contributes to beneficial anti-tumor effects whereas lower doses increase the total antioxidant capacity of cancer cells and antagonize the effects of chemo drugs. Short-term treatment with quercetin was beneficial against cancer while long-term treatment was not in studies from 2005.
Malignant mesothelioma is an asbestos-associated cancer that responds poorly to chemo drugs because of the resistance that develops to the actions of these drugs. However, the Korean scientists studied whether or not quercetin could activate the Nrf-2 pathway in malignant mesothelioma cells and cause positive changes that might improve cancer.
They found that their cancer research-oriented experiments in the laboratory showed that quercetin targeted the Nrf-2 pathway and caused the killing of mesothelioma cells, and it was a potential and efficient way to overcome resistance to some chemotherapy drugs and enhance their efficacy. Their hope now is to develop guidelines on antioxidant supplementation in cancer therapy in animal or human studies.
Lee, Yoon-Jin, Lee, David M., and Lee, Sang-Han. Nrf2 Expression and Appotosis in Quercetin-Treated Mesothelioma Cells. Mol Cells 2015 May 31;38(5):416-425.
Martin, Lauren, M.S., C.N.S., and Thiel, Anne, N.D. Quercetin in Food as Compared to Supplementation. Integrative Therapeutics, 3/16/2017. https://www.integrativepro.com/Resources/Integrative-Blog/2017/Quercetin-Food-Compared-Supplementation