Mensacarcin, a secondary metabolite isolated from Streptomyces bottropensis, was found to cause genetic instability, a hallmark of early apoptosis, in melanoma cells. This finding could lead to the development of an effective therapy to manage melanoma, according to a paper published recently in Journal of Biological Chemistry by scientists from Oregon State University.
"Mensacarcin has potent anticancer activity, with selectivity against melanoma cells," Sandra Loesgen, assistant professor of chemistry explained. "It shows powerful anti-proliferative effects in all tested cancer cell lines in the U.S. 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."
To see what mensacarcin was doing to melanoma on a subcellular level, Loesgen and her team synthesized a fluorescent mensacarcin probe. "The probe was localized to mitochondria within 20 minutes of treatment," she said. "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," she added. Subsequent experiments revealed that mensacarcin rapidly alters mitochondrial pathways, resulting in mitochondrial dysfunction, which activates pathways to apoptosis.