title: 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.
authors.affiliation: Engineering Research Centre of Industrial Microbiology, Ministry of Education, College of Life Sciences, Fujian Normal University , Fuzhou, Fujian 350117, People's Republic of China.
authors.forename: Yongbiao
authors.initials: Y
authors.lastname: Zheng
authors.forename: Haiyue
authors.initials: H
authors.lastname: Pang
authors.forename: Jifeng
authors.initials: J
authors.lastname: Wang
authors.forename: Guowei
authors.initials: G
authors.lastname: Shi
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Huang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D003470:Culture Media / Q000737:chemistry; D006801:Humans; D025282:Mycelium / Q000737:chemistry / Q000254:growth & development*; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D010945:Plants, Edible / Q000737:chemistry / Q000254:growth & development; D020076:Pleurotus / Q000737:chemistry* / Q000254:growth & development; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014675:Vegetables / Q000737:chemistry / Q000254:growth & development
chemical_list: D051017:Apoptosis Regulatory Proteins; D003470:Culture Media; D010936:Plant Extracts; D012717:Sesquiterpenes
keywords: Pleurotus cystidiosus; apoptosis inducing; edible fungus; sesquiterpenoids