Mensacarcin is a highly oxygenatedpolyketide first isolated from soil-dwellingStreptomyces bottropensis bacteria.[1][2]
The molecule is asecondary metabolite, and can be obtained in large amounts from its producing organism.[2]
Due to its unique properties it is an important model for drug development againstmelanoma and othercancers.
InNCI-60 anti-cancer compound screening mensacarcin has a highcytostatic effect against almost all cell lines (mean of 50% growth inhibition) and a relatively selectivecytotoxic effect against melanoma cells.[1]
LowCOMPARE correlation with standard antitumor agents indicate a unique mechanism of action.[1]Further examinations reveal mensacarcin effecting themitochondria.
With its unique mechanism,effective also inBRAFV600E mutationcell lines,mensacarcin is a promising model for the development of new anticancer drugs.
Existing therapies for melanoma are limited.Mensacarcin's powerful effect against melanoma cells make it especially valuable for this disease.
Mitochondria provide most of the energy used byeukaryotic cells.
In a study at the Oregon State University a synthesizedfluorescent probe of mensacarcin was localized to the mitochondria within 20 minutes of treatment.[1]
Live-cellbioenergeticflux analysis showed rapid disturbance of energy production and of mitochondrial function.[1]
The localization together with the metabolic effects provide evidence that mensacarcin targets mitochondria.
Mitochondria are also important incell death signaling.
Mensacarcin in melanoma cells activatesapoptotic pathways related tocaspase 3 andcaspase 7, and thus induces cell death.[1]
After mensacarcin treatment of two melanoma cell lines, the cells showed characteristicchromatincondensation as well as distinctpoly(ADP-ribose)polymerase-1 cleavage;flow cytometry identified a large population of apoptotic cells;single-cellelectrophoresis indicated that mensacarcin causesgenetic instability, a sign of early apoptosis.[1]
The BRAF V600E mutation is associated with drug resistance.[1]Due to its independent mechanism, mensacarcin has an undiminished effect in melanoma cell lines with this mutation (NCI 60 cell linesSK-Mel-28 andSK-Mel-5).[1]