title: Ganoderic acid DM, a natural triterpenoid, induces DNA damage, G1 cell cycle arrest and apoptosis in human breast cancer cells.
abstract: Ganoderic acid DM (GADM) is a triterpenoid isolated from Ganoderma lucidum, a well-known edible medicinal mushroom. In the present study, we found that GADM effectively inhibited cell proliferation and colony formation in MCF-7 human breast cancer cells, which was much stronger than that of MDA-MB-231 breast cancer cells. GADM both concentration- and time-dependently mediated G1 cell cycle arrest and significantly decreased the protein level of CDK2, CDK6, cycle D1, p-Rb and c-Myc in MCF-7 cells. Moreover, GADM obviously induced DNA fragmentation and cleavage of PARP which are the characteristics of apoptosis and decreased the mitochondrial membrane potential in MCF-7 cells. Besides, we also showed that GADM elicited DNA damage as measured by comet assay which is a sensitive method for DNA damage detection. γ-H2AX, a marker of DNA damage, was also slightly up-regulated after treated with GADM for 6h, suggesting that the G1 cell cycle arrest and apoptosis induced by GADM may be partially resulted from GADM-induced DNA damage. These results have advanced our current understandings of the anti-cancer mechanisms of GADM.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine (University of Macau), Macao, PR China.
authors.forename: Guo-Sheng
authors.initials: GS
authors.lastname: Wu
authors.forename: Jin-Jian
authors.initials: JJ
authors.lastname: Lu
authors.forename: Jia-Jie
authors.initials: JJ
authors.lastname: Guo
authors.forename: Ying-Bo
authors.initials: YB
authors.lastname: Li
authors.forename: Wen
authors.initials: W
authors.lastname: Tan
authors.forename: Yuan-Ye
authors.initials: YY
authors.lastname: Dang
authors.forename: Zhang-Feng
authors.initials: ZF
authors.lastname: Zhong
authors.forename: Zeng-Tao
authors.initials: ZT
authors.lastname: Xu
authors.forename: Xiu-Ping
authors.initials: XP
authors.lastname: Chen
authors.forename: Yi-Tao
authors.initials: YT
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006657:Histones / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D020940:Reishi / Q000737:chemistry*; D013234:Stem Cells; D013997:Time Factors; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C468783:H2AX protein, human; D006657:Histones; D014315:Triterpenes; C556862:ganoderic acid