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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

  • Molecular Toxicology
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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 μg/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 NFκB 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.

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Abbreviations

DR:

Death receptor

EEAC:

Extracts of fruiting bodies of Antrodia camphorata

FLIP:

FLICE inhibitory protein

HAT:

Histone acetyltransferase

HDACIs:

Histone deacetylase inhibitors

MTT:

3-(4, 5-Dimethylthiazol-2-yl)–2,5-diphenyltetrazolium bromide

NFκB:

Nuclear factor kappa B

PARP:

Poly(ADP-ribose) polymerase

TRADD:

Tumor necrosis factor (TNF)-receptor 1-associated death domain protein

TRAIL:

TNF-related apoptosis-inducing ligand

TSA:

Trichostatin A

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Acknowledgments

The authors would like to thank Dr. Hung-Liang Lay, National Pingtung University of Science and Technology, Taiwan, for identification of wild fruiting bodies of Antrodia camphoarata, and the National Science Council, Taiwan, for financial support.

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Correspondence to Fang-Rong Chang or Yang-Chang Wu.

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Lu, MC., Du, YC., Chuu, JJ. et al. 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. Arch Toxicol 83, 121–129 (2009). https://doi.org/10.1007/s00204-008-0337-3

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