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.

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.
AuthorsMei-Chin Lu, Ying-Chi Du, Jiunn-Jye Chuu, Shiuh-Lin Hwang, Pao-Chuan Hsieh, Chih-Sheng Hung, Fang-Rong Chang, Yang-Chang Wu
JournalArchives of toxicology (Arch Toxicol) Vol. 83 Issue 2 Pg. 121-9 (Feb 2009) ISSN: 1432-0738 [Electronic] Germany
PMID18709356 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • Histones
  • Hydroxamic Acids
  • NF-kappa B
  • Plant Extracts
  • Receptors, Death Domain
  • trichostatin A
  • Antrodia (chemistry)
  • Apoptosis (drug effects)
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Cell Survival (drug effects)
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Drug Therapy, Combination
  • Enzyme Activation (drug effects)
  • Enzyme Inhibitors (pharmacology)
  • Gene Expression Regulation, Neoplastic (drug effects)
  • HL-60 Cells
  • Histone Deacetylase Inhibitors
  • Histones (metabolism)
  • Humans
  • Hydroxamic Acids (pharmacology, toxicity)
  • Leukemia (drug therapy)
  • NF-kappa B (metabolism)
  • Plant Extracts (pharmacology)
  • Receptors, Death Domain (drug effects, metabolism)

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