Researchers have discovered that a type of bacterium that lives in soil produces a molecule that actually induces the death of melanoma cells. This molecule is made as a metabolite of Streptomyces bottropensis; it is a natural product and is generated in abundance. There are very few useful treatment options for melanoma, which is the deadliest type of skin cancer; as such, this work, reported in the Journal of Biological Chemistry, could be very significant.
There are over 80,000 new cases of melanoma diagnosed every year, and around 9,000 people die from the disease in the United States alone. There is variation among races and ethnicities, but the lightest skin tones are at highest risk according to the Centers for Disease Control and Prevention (CDC).
The researchers, Sandra Loesgen, assistant professor of chemistry, Terence Bradshaw, a scholar in the College of Science at OSU, postdoctoral fellow Birte Plitzko and graduate candidate Elizabeth Kaweesa found that the natural chemical, mensacarcin, can attack melanoma's mitochondria, an organelle in cells that produces power. The melanoma cells need them to live.
Mitochondria also have a role in the signals surrounding cell death. They have been seen as a potential therapeutic target because the mitochondria of cancer cells have a different structure and function than the mitochondria found in non-cancerous cells.
"Mensacarcin has potent anticancer activity, with selectivity against melanoma cells," Loesgen noted. "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."
The researchers wanted to know how mensacarcin acted on melanoma on the subcellular level, so they created a fluorescent probe to follow it. "The probe was localized to mitochondria within 20 minutes of treatment," she revealed. "The localization together with mensacarcin's unusual metabolic effects in melanoma cells provide evidence that mensacarcin targets mitochondria."
Further analysis of the bioenergetic changes illustrated how mensacarcin rapidly disrupted the function of mitochondria, and thus, the production of energy. "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."
The disorder initiates pathways to cell death or apoptosis. "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," Loesgen explained. "Mensacarcin's unique mode of action indicates it might represent a promising lead for the development of new anticancer drugs."
Learn more about the prevention and control of skin cancer from the video above by the CDC.
Sources: AAAS/Eurekalert! Via OSU, CDC, Journal of Biological Chemistry