Skyrin (SKR) is a plant bisanthraquinone secondary metabolite from the Hypericum genus with potential use in anticancer therapy. However, its effect and mechanism of action are still unknown. The negative effect of SKR on HCT 116 and HT-29 cancer cell lines in hypoxic and normoxic conditions was observed. HCT 116 cells were more responsive to SKR treatment as demonstrated by decreased metabolic activity, cellularity and accumulation of cells in the G1 phase. Moreover, an increasing number of apoptotic cells was observed after treatment with SKR. Based on the LC-MS comparative proteomic data from hypoxia and normoxia (data are available via ProteomeXchange with the identifier PXD019995), SKR significantly upregulated Death receptor 5 (DR5), which was confirmed by real-time qualitative PCR (RT-qPCR). Furthermore, multiple changes in the Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-activated cascade were observed. Moreover, the reversion of TRAIL resistance was observed in HCT 116, HT-29 and SW620 cell lines, even in hypoxia, which was linked to the upregulation of DR5. In conclusion, our results propose the use of SKR as a prospective anticancer drug, particularly as an adjuvant to TRAIL-targeting treatment to reverse TRAIL resistance in hypoxia.

• Keywords
• Death receptor 5, Hypericum, TRAIL, TRAIL resistance, colorectal cancer, hypoxia, proteomics, skyrin,
• Publication type
• Journal Article MeSH

A new metabolite was isolated from the culture of Penicillium rugulosum and its structure was determined from physico-chemical data. Accompanying metabolites skyrin and rugulosin were characterized by UV, IR, CD, mass and NMR spectra.

• MeSH
• Pigments, Biological biosynthesis   MeSH
• Chemical Phenomena MeSH
• Chemistry MeSH
• Naphthoquinones analogs & derivatives   biosynthesis   MeSH
• Penicillium metabolism   MeSH
• Soil Microbiology * MeSH
• Spectrum Analysis MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Pigments, Biological MeSH
• Naphthoquinones MeSH

Two new species, Penicillium krskae (isolated from the air as a lab contaminant in Tulln (Austria, EU)) and Penicillium silybi (isolated as an endophyte from asymptomatic milk thistle (Silybum marianum) stems from Josephine County (Oregon, USA)) are described. The new taxa are well supported by phenotypic (especially conidial ornamentation under SEM, production of red exudate and red pigments), physiological (growth at 37 °C, response to cycloheximide and CREA), chemotaxonomic (production of specific extrolites), and multilocus phylogenetic analysis using RNA-polymerase II second largest subunit (RPB2), partial tubulin (benA), and calmodulin (CaM). Both new taxa are resolved within the section Exilicaulis in series Restricta and show phylogenetic affiliation to P. restrictum sensu stricto. They produce a large spectrum of toxic anthraquinoid pigments, namely, monomeric anthraquinones related to emodic and chloremodic acids and other interesting bioactive extrolites (i.e., endocrocin, paxilline, pestalotin, and 7-hydroxypestalotin). Of note, two bianthraquinones (i.e., skyrin and oxyskyrin) were detected in a culture extract of P. silybi. Two new chloroemodic acid derivatives (2-chloro-isorhodoptilometrin and 2-chloro-desmethyldermoquinone) isolated from the exudate of P. krskae ex-type culture were analyzed by nuclear magnetic resonance (NMR) and liquid chromatography-mass spectrometry (LC-MS).

• Keywords
• Penicillium restrictum group, cycloheximide tolerance, milk thistle, mycotoxins, red exudate, secondary metabolites,
• Publication type
• Journal Article MeSH