title: Structure, cytotoxic activity and mechanism of protoilludane sesquiterpene aryl esters from the mycelium of Armillaria mellea.
abstract: BACKGROUND
  Armillaria mellea (Vahl. ex. Fr.) Karst is an important traditional Chinese medicine used in dispelling wind and removing obstruction in the meridians, and strengthening tendons and bones. Armillaria mellea has been recorded in the book Caobenshiyi which was written by ancestor for the function of suppressing hyderactive liver for calming endogenous wind medicine. The aim of this study is to investigate the cytotoxic activity for liver cell lines (normal and cancerous) of protoilludane sesquiterpene aryl esters from the mycelium of A. mellea.
  
  
  METHODS
  A systemic fractionation of the mycelium extracts of A. mellea and relative activity mechanisms were studied.
  
  
  RESULTS
  Two new protoilludane sesquiterpene aryl esters named 5'-methoxy-armillasin (1) and 5-hydroxyl-armillarivin (2) were isolated. In addition, eight known protoilludane sesquiterpene aryl esters armillaridin (3), armillartin (4), armillarin (5), melleolide B (6), armillarilin (7), armillasin (8), armillarigin (9) and melleolide (10) were also isolated from the mycelium of A. mellea. The relative configurations of the two new compounds were confirmed by NOESY spectra. Among ten protoilludane sesquiterpene aryl esters, compounds 2, 3, 4, 7, 8, 9 and 10 were active constituents with highly cytotoxic activity against HepG2 cells (4.95-37.65μg/mL). We reported here for the time, that compound 10 (melleolide) showed anti-tumor ability on hepatoma cell. The relative mechanism was assessed on HepG2 cells.
  
  
  CONCLUSIONS
  Among all the ten protoilludane sesquiterpene aryl esters, melleolide (10) showed the best cytotoxic activity for HepG2 cells (4.95μg/mL) and lower activity for L02 cells (16.05μg/mL). Mechanism study showed that melleolide decreased the viability of the cancer cells with varying levels of cleaved-caspase 3, caspase 8, caspase 9, Bax and Ki67 expression. On the other hand, melleolide induced HepG2 cell cycle arrest at the G2/M phase.
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China.
authors.forename: Zhijin
authors.initials: Z
authors.lastname: Li
authors.affiliation: Shijiazhuang No.4 Pharmaceutical Co., ltd, Shijiazhuang 050000, China.
authors.forename: Yunchao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Jiang
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China; School of Pharmaceutical Science, Jilin Medical University, Jilin 132013, China. Electronic address: liwl100@nenu.edu.cn.
authors.forename: Wenliang
authors.initials: W
authors.lastname: Li
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Zheng
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Yang
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China.
authors.forename: Yongli
authors.initials: Y
authors.lastname: Bao
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China.
authors.forename: Luguo
authors.initials: L
authors.lastname: Sun
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China.
authors.forename: Yanxin
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Jilin Province Key Laboratory on Chemistry and Biology of Natural Drugs in Changbai Mountain, School of life Sciences, Northeast Normal University, Changchun 130024, China. Electronic address: yxli486@126.com.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D055392:Armillaria; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004952:Esters; D006801:Humans; D015394:Molecular Structure; D025282:Mycelium / Q000737:chemistry; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D004952:Esters; D012717:Sesquiterpenes
keywords: Armillaria mellea; Armillaridin (PubChem CID: 126031); Armillarigin (PubChem CID: 51351607); Armillarilin (PubChem CID: 195529); Armillarin (PubChem CID: 134206); Armillartin (PubChem CID: 131866); Armillasin (PubChem CID: 134206); Cytotoxic activity; Melleolide; Melleolide (PubChem CID: 435402); Protoilludane Sesquiterpene aryl esters