Soil Bacterium Could Be Potentially Effective Against Melanoma
In the U.S. alone, more than 80,000 new melanoma cases are diagnosed each year, and about 9000 melanoma patients die. Men are more likely than women to develop melanoma; the death rate varies by race and ethnicity and is highest among Caucasians.
Now, a team from the Oregon State University has upon investigation come across a type of soil-dwelling bacterium that produces molecules that are capable of inducing death in melanoma cells.
The molecule the OSU team recently identified—called mensacarcin—is a natural product and secondary metabolite from the soil bacteria Streptomyces bottropensis. Mensacarcin is a highly oxidized and stereogenic complex molecule that can be obtained in large amounts from these bacteria. The properties of this compound are important as there are few thera
pies that effectively manage melanoma, the most dangerous form of skin cancer.“Mensacarcin has potent anticancer activity, with selectivity against melanoma cells,” explained senior study investigator Sandra Loesgen, Ph.D., assistant professor of chemistry at OSU. “It shows powerful antiproliferative effects in all tested cancer cell lines in the U.S. National Cancer Institute’s cell line panel, but inhibition of cell growth is accompanied by fast progression into cell death in only a small number of cell lines, such as melanoma cells.”
The team synthesized a fluorescent mensacarcin probe to test this molecule at a subcellular level. The probe was localized to mitochondria within 20 minutes of treatment. The researchers found that the localization together with mensacarcin’s unusual metabolic effects in melanoma cells provide evidence that mensacarcin targets mitochondria. Live-cell bioenergetic flux analysis showed mensacarcin disturbed energy production and mitochondrial function rapidly.
“Its unique mode of action suggests it may be a useful probe for examining energy metabolism,” Dr. Loesgen noted. “Subsequent experiments revealed that mensacarcin rapidly alters mitochondrial pathways, resulting in mitochondrial dysfunction.”
After careful analysis, the researchers found that mensacarcin’s action within mitochondria leads to the activation of apoptotic pathways in melanoma cells.
“Flow cytometry identified a large population of apoptotic melanoma cells, and single-cell electrophoresis indicated that mensacarcin causes genetic instability, a hallmark of early apoptosis,” Dr. Loesgen concluded. “Mensacarcin’s unique mode of action indicates it might represent a promising lead for the development of new anticancer drugs.“
