Chemotherapy and radiation are very ineffective when being used on melanoma skin cancer or glioblastoma multiforme brain cancer. The department of nutritional sciences at the University of Arizona has a very intense interest in both forms of cancer and wants to find how quercetin, a natural, biologically-active compound is capable of sensitizing the cancerous tumors to treatment and not harm normal tissue. This research has become very important as the occurrence of melanoma, often a fatal form of skin cancer, is growing at the rate of three percent per year according to the American Cancer Society.
The standard chemotherapeutic drug used to treat melanoma cancer has been proven ineffective over the years of use when used by itself. Randy Burd, assistant professor of nutritional sciences and a member of The University of Arizona BIO Institute, and his team are testing the drug, as well as its new analog Temozolomide. They are being tested with a variety of biochemical backbones and plant compounds. They then analyzed the enzymes involved in their activation. They worked with COX-2 inhibitors and found they each had their own complications so they started looking at quinones, which can be found in nature as pigments, vitamin biochemical backbones and plant compounds.
Quercetin is a polyphenol that is found in fruits and vegetables, a quinone, and it has demonstrated it has an exciting effect on melanoma tumors. If quercetin is used in low concentrations, it acts as an antioxidant but if it is used in high concentrations, it changes to a cell-damaging pro-oxidant. The study is taking advantage of this pro-oxidant character of quercetin. Burd’s team is using tyrosinase as a highly expressed enzyme responsible for the pigment formation in human skin cells which grow out-of-control in melanoma. Burd commented that quercetin is similar to precursors of melanin, and so tyrosinase identifies and stimulates quercetin to a pro-oxidant rather than an antioxidant. Quercetin, when it is tested with melanoma tumor-cell cultures, the tumor cells die. This happens because the melanoma enzyme is tricked into stimulating so much quercetin that it changes and sensitizes the cancerous melanoma cells to the chemotherapy drug and dies. In this situation, quercetin is acting as a biological response modifier. A response modifier is a drug or a chemical compound acting to change the function of tumor cells to make them more responsive to chemotherapy or radiation.
Burd’s team is now analyzing a group of bioactive food and plant substances to see if they can find out if they will kill tumor cells for different cancers. If they do, they want to discover the genes or proteins involved in this action. Successful compounds like the quercetin used in the melanoma study, need to be modified by scientists so they can be made into functional pharmaceutical drugs. This will make the compounds more influential and each of them can be tested in clinical trials. The goal of this work is to find quercetin combinations so they can design a specific therapy for each cancer type that has been successful in their research.
Glioblastoma multiforme brain cancer research has one fundamental focus and that is to find and screen quinones which can be used in the brain to reverse the radiation-resistance of tumors. Those compounds would then be in conjunction with radiation treatment. This approach is new and much has to be done before they are ready to develop successful pharmaceutical drugs.