New Monascus metabolites: structure elucidation and toxicological properties studied with immortalized human kidney epithelial cells.
Monascus sp. are used for the production of red yeast rice, which has been applied in Asian food and medicine for centuries. The fungi form several secondary metabolites, among others the monascopyridines A and B. We have now detected two new monascopyridines (named C and D) with similar UV absorption spectra and maxima at 306-307 nm in red rice fermented with M. purpureus. The new monascopyridines have the same chromophores as the already known and differ in a missing gamma-lactone ring only. Monascopyridine C has a hexanoyl side chain, whereas monascopyridine D is the higher homologue with an octanoyl side chain. The toxicological properties of monascopyridines were studied using immortalized human kidney epithelial cells, displaying cytotoxic effects in micromolar concentrations with median effective concentration values between 20.7 and 43.2 micromol/L, depending on the compound and method used. The monascopyridines C and D did not induce apoptosis. However, they caused a rise of the mitotic index from 3.21 +/- 0.27% (control) to maximum 8.14 +/- 0.89% (monascopyridine D) by an accumulation of cells in the metaphase with a simultaneous decrease of cells in the ana- and telophase. Monascopyridine-induced metaphase arrest is caused by a partial or complete loss of the spindle apparatus as indicated by the occurrence of abnormal metaphases and immunological staining of alpha-tubulin. These effects are indicating an aneuploidic potential and therefore the monascopyridines C and D might contribute to tumor formations.
Knecht
Anja
A
Institut für Lebensmittelchemie, Westfälische Wilhelms-Universität Münster, Germany.
Cramer
Benedict
B
Humpf
Hans-Ulrich
HU
D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002461:Cell Line, Transformed; D002851:Chromatography, High Pressure Liquid; D004847:Epithelial Cells; D005285:Fermentation; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry* / Q000633:toxicity*; D007668:Kidney; D009682:Magnetic Resonance Spectroscopy; D032741:Monascus / Q000378:metabolism*; D012275:Oryza / Q000737:chemistry* / Q000382:microbiology; D012639:Seeds / Q000737:chemistry
D007546:Isoquinolines; C510386:monascopyridine C; C510387:monascopyridine D; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases