Selenium Boosts Potency of Anti-Melanoma Compounds

Drug developers have improved on nature by modifying a naturally occurring anti-melanoma compound so that it becomes significantly more potent in fighting the disease.

Investigators at the Pennsylvania State College of Medicine (Hershey, USA) sought to increase the anticancer potency of isothiocyanates, which are a family of compounds derived from horseradish, radishes, onions, and mustards, and are the source of the hotness of those plants and preparations.

Capitalizing on previous results that showed the anticancer properties of selenium they modified naturally occurring isothiocyanates by using the isothiocyanate backbone but increasing the alkyl chain length and replacing a sulfur atom with selenium. They coined the term "isoselenocyanates" to describe the new compounds.

To test the isoselenocyanate compounds in a model system for melanoma, they injected immunocompromised mice with 10 million melanoma cells. Six days later, when the animals had developed large tumors, they were divided into two groups and treated separately with either natural isothiocyanates or with the complementary isoselenocyanates.

Results published in the March 2009 edition of the journal Clinical Cancer Research revealed that the isoselenocyanates decreased tumor development by nearly 60% compared with the corresponding isothiocyanates, which had no effect. No changes in animal body weight or in blood parameters indicative of liver-, kidney-, or cardiac-related toxicity were observed with the isoselenocyanates.

The positive effect of the isoselenocyanates was traced to their inhibition of the Akt3 protein, which is increased in about 70% of tumors where it decreases apoptosis in order to promote tumorigenesis.

"There are currently no drugs to target the proteins that trigger melanoma," said senior author Dr. Gavin Robertson, associate professor of pharmacology, pathology, and dermatology at the Pennsylvania State College of Medicine. "We have developed drugs from naturally occurring compounds that can inhibit the growth of tumors in mice by 50 to 60% with a very low dose. We have harnessed something found in nature to target melanoma, and since we only need tiny amounts to kill the cancer cells, it means even less toxic side-effects for the patient."

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Pennsylvania State College of Medicine