Scientists Find Compounds That Sensitize Cancerous Tumors To Therapy

Scientists Find Compounds That Sensitize Cancerous Tumors To Therapy
Melanoma, an aggressive form of skin cancer, and glioblastoma multiforme brain cancer respond very poorly to chemotherapy and radiation, says study.
Now, scientists at The University of Arizona are attempting to find natural, biologically active compounds that will sensitize the cancerous tumors to therapy without damaging normal tissue.

By using the compounds in conjunction with conventional treatment, the researchers hope patient survival rates will ultimately increase.

Dacarbazine, the standard chemotherapeutic drug for melanoma for decades, has been ineffective when used alone.

To improve its performance, Randy Burd, assistant professor of nutritional sciences and member of the UA's BIO5 Institute, has been testing the drug and its new analog Temozolomide in combination with various bioactive compounds to gain greater response rates on melanoma tumors in cell cultures.

"After working with COX-2 inhibitors - which had complications - we started looking at quinones, which occur in nature as pigments, vitamin biochemical backbones and plant compounds, and then we analyzed the enzymes involved in their activation," Burd said.

Quercetin, a polyphenol found in apples, onions, green tea and other plant-based foods, is a quinone that has shown an interesting effect on melanoma tumors.

In low concentrations, quercetin behaves as an antioxidant, yet at high concentrations it becomes a cell-damaging pro-oxidant.

Burd's team is exploiting the pro-oxidant attribute of quercetin, using tyrosinase, which is the highly expressed enzyme responsible for the pigment formation in human skin cells that grow out of control in melanoma.

"The quercetin is similar to precursors of melanin. The tyrosinase actually recognizes and activates quercetin to a pro-oxidant rather than an antioxidant," Burd said.

When tested together in melanoma tumor cell cultures, the result is tumor cell death. The melanoma enzyme is tricked into activating so much quercetin that it turns around and sensitizes the melanoma cells to the chemotherapy drug, and they die.

According to Burd, Quercetin is an example of a biological response modifier, which is a drug or a compound that changes the function of tumor cells so they will be more responsive to chemotherapy or radiation.

In the case of glioblastoma multiforme brain cancer, the focus is on finding and screening quinones that could be used in the brain to reverse the radiation-resistance of tumors, and then using those compounds in conjunction with radiation treatment.


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