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

作者：Lu Mei Chin; Du Ying Chi; Chuu Jiunn Jye; Hwang Shiuh Lin; Hsieh Pao Chuan; Hung Chih Sheng; Chang Fang Rong^*; Wu Yang Chang

来源：Archives of Toxicology, 2009, 83(2): 121-129.

DOI：10.1007/s00204-008-0337-3

• Antrodia camphorata (AC)
• Death receptor (DR)
• Histone acetylation
• Nuclear factor kappa B (NF kappa B)
• Trichostatin A (TSA)
• Zhankuic acid 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 mu g/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 NF kappa B 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.

• 出版日期2009-2