New Apoptosis-Inducing Sesquiterpenoids from the Mycelial Culture of Chinese Edible Fungus Pleurotus cystidiosus

Abstract

Two new bisabolane-type sesquiterpenoids, pleuroton A (1) and pleuroton B (2), and three clitocybulol derivatives, clitocybulol D (3), clitocybulol E (4), and clitocybulol F (5), were obtained from the mycelial culture of edible fungus Pleurotus cystidiosus O. K. Mill by repeated column chromatography over RP-18, Sephadex LH-20, and silica gel. Their structures were determined according to nuclear magnetic resonance data, high-resolution electron impact mass spectrometry, and circular dichroism spectra. These new sesquiterpenoids exhibited significant cytotoxicity against two human prostate cancer DU-145 and C42B cells in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The median inhibitory concentration (IC50) of compounds 1, 2, 3, 4, and 5 was 174, 28, 233, 162, and 179 nM, respectively, against the DU-145 cell and was 104, 52, 163, 120, and 119 nM, respectively, against the C42B cell. Especially, pleuroton B (2) exhibited the strongest cytotoxity among these sesquiterpenoids, which was confirmed by the colony formation assay. Furthermore, pleuroton B (2) could trigger the apoptosis of DU-145 cells through the detection of apoptosis cells using annexin V-FITC staining by flow cytometry, the observation of condensed nuclei in the apoptosis cells, and the western blot analysis for the expression of apoptosis-related proteins Bcl-2, Bak, and Bax. Analysis of structure-activity relationships of these sesquiterpenoids revealed that the unusual functional moiety of pleuroton B should contribute to its significant bioactivity. These results display the pharmacological potential of P. cystidiosus.

Toward an Increased Functionality in Oyster (Pleurotus) Mushrooms Produced on Grape Marc or Olive Mill Wastes Serving as Sources of Bioactive Compounds

“…Pleurotus (oyster) mushrooms contain dietary fibers, vitamins, terpenics, statins, essential amino acids, sterols, β-glucans, and antioxidant microconstituents, which demonstrate immunomodulatory, hypoglycaemic, hypocholesterolaemic, antimicrobial, antithrombotic, antiatherogenic, anti-inflammatory, antihypertensive, antitumor, and prebiotic activities. − …”

Alliacane-Type Secondary Metabolites from Submerged Cultures of the Basidiomycete Clitocybe nebularis

“…: Fr.) Earle (formerly named Marasmius alliaceus ), featuring an epoxidized hydrindane structure with a butyrolactone moiety, was the first reports of alliacane-type sesquiterpenoids. − Further examples for secondary metabolites possessing an alliacane skeleton are the group of clitocybulols, isolated from Clitocybula oculus (clitocybulols A–C) and Pleurotus cystidiosus (clitocybulols D–O), , the purpuracolides A–C from Gomphus purpuraceus , , incarnetic acid from Gloeostereum incarnatum , and the inonoalliacanes A–I from Inonotus sp., which are to some degree structurally related to nebucanes E–G ( 5 – 7 ). Notably, these fungi belong to various different families and orders in the Agaricomycetes, and it is presently not possible to draw any conclusions on potential chemotaxonomic correlations.…”

Chemistry and Bioactivity of Marine-Derived Bisabolane Sesquiterpenoids: A Review

“…Especially, 119 exhibited the strongest effect on two human prostate cancer DU-145 and C42B cells, with the IC 50 s of 28 and 52 nM. Further pharmacological studies indicated that 119 induced the apoptosis of DU-145 cells ( Zheng et al, 2015 ). The dicyclic 141 obtained from the rhizomes of Curcuma longa displayed more potent anti-inflammatory activity against the LPS-activated production of NO (IC 50 , 25.5 μM), when compared with the positive control dexamethasone (IC 50 , 33.6 μM) ( Cheng et al, 2019 ).…”