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.
Similar content being viewed by others
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
References
Balasubramanyam K, Swaminathan V, Ranganathan A, Kundu TK (2003) Small molecule modulators of histone acetyltransferase p300. J Biol Chem 278:19134–19140
Berger SL (2002) Histone modifications in transcriptional regulation. Curr Opin Genet Dev 12:142–148
Bravo SB, Garcia-Rendueles ME, Seoane R, Dosil V, Cameselle-Teijeiro J, Lopez-Lazaro L, Zalvide J, Barreiro F, Pombo CM, Alvarez CV (2005) Plitidepsin has a cytostatic effect in human undifferentiated (anaplastic) thyroid carcinoma. Clin Cancer Res 11:7664–7673
Chen CH, Yang SW, Shen YC (1995) New steroid acids from Antrodia cinnamomea, a fungal parasite of Cinnamomum micranthum. J Nat Prod 58:1655–1661
Chen KC, Peng CC, Peng RY, Su CH, Chiang HS, Yan JH, Hsieh-Li HM (2007) Unique formosan mushroom Antrodia camphorata differentially inhibits androgen-responsive LNCaP and -independent PC-3 prostate cancer cells. Nutr Cancer 57:111–121
Chiu HH (2007) Phylogenetic analysis of Antrodia species and Antrodia camphorata inferred from internal transcribed spacer region. Antonie Van Leeuwenhoek 91:267–276
Hsu YL, Kuo YC, Kuo PL, Ng LT, Kuo YH, Lin CC (2005) Apoptotic effects of extract from Antrodia camphorata fruiting bodies in human hepatocellular carcinoma cell lines. Cancer Lett 221:77–89
Hsu YL, Kuo PL, Cho CY, Ni WC, Tzeng TF, Ng LT, Kuo YH, Lin CC (2007) Antrodia cinnamomea fruiting bodies extract suppresses the invasive potential of human liver cancer cell line PLC/PRF/5 through inhibition of nuclear factor kappaB pathway. Food Chem Toxicol 45:1249–1257
Kang J, Chen J, Shi Y, Jia J, Zhang Y (2005) Curcumin-induced histone hypoacetylation: the role of reactive oxygen species. Biochem Pharmacol 69:1205–1213
Kang J, Chen J, Zhang D, Da W, Ou Y (2004) Synergistic killing of human leukemia cells by antioxidants and trichostatin A. Cancer Chemother Pharmacol 54:537–545
Lin SB, Li CH, Lee SS, Kan LS (2003) Triterpene-enriched extracts from Ganoderma lucidum inhibit growth of hepatoma cells via suppressing protein kinase C, activating mitogen-activated protein kinases and G2-phase cell cycle arrest. Life Sci 72:2381–2390
Liu DZ, Liang YC, Lin SY, Lin YS, Wu WC, Hou WC, Su CH (2007) Antihypertensive activities of a solid-state culture of Taiwanofungus camphoratus (Chang-chih) in spontaneously hypertensive rats. Biosci Biotechnol Biochem 71:23–30
Lu MC, Yang SH, Hwang SL, Lu YJ, Lin YH, Wang SR, Wu YC, Lin SR (2006) Induction of G2/M phase arrest by squamocin in chronic myeloid leukemia (K562) cells. Life Sci 78:2378–2383
Peng CC, Chen KC, Peng RY, Chyau CC, Su CH, Hsieh-Li HM (2007) Antrodia camphorata extract induces replicative senescence in superficial TCC, and inhibits the absolute migration capability in invasive bladder carcinoma cells. J Ethnopharmacol 109:93–103
Ruefli AA, Ausserlechner MJ, Bernhard D, Sutton VR, Tainton KM, Kofler R, Smyth MJ, Johnstone RW (2001) The histone deacetylase inhibitor and chemotherapeutic agent suberoylanilide hydroxamic acid (SAHA) induces a cell-death pathway characterized by cleavage of Bid and production of reactive oxygen species. Proc Natl Acad Sci USA 98:10833–10838
Schwab M, Reynders V, Loitsch S, Steinhilber D, Stein J, Schroder O (2007) Involvement of different nuclear hormone receptors in butyrate-mediated inhibition of inducible NF kappa B signalling. Mol Immunol 44:3625–3632
Sheikh MS, Huang Y (2004) Death receptors as targets of cancer therapeutics. Curr Cancer Drug Targets 4:97–104
Shetty S, Graham BA, Brown JG, Hu X, Vegh-Yarema N, Harding G, Paul JT, Gibson SB (2005) Transcription factor NF-kappaB differentially regulates death receptor 5 expression involving histone deacetylase 1. Mol Cell Biol 25:5404–5416
Song TY, Hsu SL, Yeh CT, Yen GC (2005) Mycelia from Antrodia camphorata in Submerged culture induce apoptosis of human hepatoma HepG2 cells possibly through regulation of Fas pathway. J Agric Food Chem 53:5559–5564
Swarup V, Das S, Ghosh S, Basu A (2007) Tumor necrosis factor receptor-1-induced neuronal death by TRADD contributes to the pathogenesis of Japanese encephalitis. J Neurochem 103:771–783
Taplick J, Kurtev V, Lagger G, Seiser C (1998) Histone H4 acetylation during interleukin-2 stimulation of mouse T cells. FEBS Lett 436:349–352
Tsai ZT, Liaw SL (1982) The use and the effect of Ganoderma. Sheng-Yun Publisher Inc, Taichung, Taiwan, pp 116–117
Vandergeeten C, Quivy V, Moutschen M, Van Lint C, Piette J, Legrand-Poels S (2007) HIV-1 protease inhibitors do not interfere with provirus transcription and host cell apoptosis induced by combined treatment TNF-alpha + TSA. Biochem Pharmacol 73:1738–1748
Wu H, Pan CL, Yao YC, Chang SS, Li SL, Wu TF (2006) Proteomic analysis of the effect of Antrodia camphorata extract on human lung cancer A549 cell. Proteomics 6:826–835
Yang S-W, Shen Y-C, C-Hsiung Chen (1996) Steroids and triterpenoids of Antodia cinnamomea–a fungus parasitic on Cinnamomum micranthum. Phytochemistry 41:1389–1392
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.
Author information
Authors and Affiliations
Corresponding authors
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00204-008-0337-3