title: Active extracts of wild fruiting bodies of Antrodia camphorata (EEAC) induce leukemia HL 60 cells apoptosis partially through histone hypoacetylation and synergistically promote anticancer effect of trichostatin A.
abstract: The endemic species of Antrodia camphorate (AC) is a promising chemotherapeutic drug for cancer. We found that the ethanol extract from wild fruiting bodies of Antrodia camphorata (EEAC) could induce HL 60 cells apoptosis via histone hypoacetylation, up-regulation of histone deacetyltransferase 1 (HDAC 1), and down-regulation of histone acetyltransferase activities including GCN 5, CBP and PCAF in dose-dependent manner. In combination with histone deacetylase inhibitor, trichostatin A (TSA), did not block EEAC-induced apoptosis. Interestingly, combined treatment (100 nM of TSA and 100 microg/ml EEAC) caused synergistic inhibition of cell growth and increase of apoptotic induction. EEAC could effectively increase the cytotoxic sensitivity of TSA through the up-regulation of DR5 and NFkappaB activation. In this present study, bioassay-guided fractionation of EEAC led to a major active compound, zhankuic acid A, as the bioactive marker. Moreover, our findings may represent an experimental basis for developing EEAC as a potential chemotherapeutic adjuvant.
authors: Graduate Institute of Natural Products, School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan. Jinx6609@yahoo.com
authors: Mei-Chin
authors: MC
authors: Lu
authors: Ying-Chi
authors: YC
authors: Du
authors: Jiunn-Jye
authors: JJ
authors: Chuu
authors: Shiuh-Lin
authors: SL
authors: Hwang
authors: Pao-Chuan
authors: PC
authors: Hsieh
authors: Chih-Sheng
authors: CS
authors: Hung
authors: Fang-Rong
authors: FR
authors: Chang
authors: Yang-Chang
authors: YC
authors: Wu
mesh_terms: D055491:Antrodia / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018922:HL-60 Cells; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology* / Q000633:toxicity; D007938:Leukemia / Q000188:drug therapy*; D016328:NF-kappa B / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D053218:Receptors, Death Domain / Q000187:drug effects / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D016328:NF-kappa B; D010936:Plant Extracts; D053218:Receptors, Death Domain; C012589:trichostatin A