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.

Review of Pharmacological Effects of Antrodia camphorata and Its Bioactive Compounds

“…Furthermore, AC-SS showed its adjuvant effects through the inhibition of MDR gene expressions and the pathway of COX-2-dependent inhibition of AKT phosphorylation [47]. In terms of the very recent literature, Lu et al [48] noted that ethanol extract from wild fruiting bodies of A. camphorata (EEAC) dose-dependently induced human premyelocytic leukemia HL 60 cells apoptosis via histone hypoacetylation, upregulation of histone deacetyltransferase 1 (HDAC 1), and downregulation of histone acetyltransferase activities including GCN 5, CBP and PCAF. Furthermore, combined treatment with 100 nM of trichostatin A (histone deacetylase inhibitor) and 100  μ g ml −1 EEAC caused synergistic inhibition of cell growth and increase of apoptotic induction through the upregulation of DR5 and NF- κ B activation [48].…”

Zhankuic acid A as a novel JAK2 inhibitor for the treatment of concanavalin A-induced hepatitis

“…The mechanisms of action of ZAA are complex, including integrating pro-apoptotic effects, inhibition of proliferation, and DNA damage [33][34][35]. Although much information is available regarding the anti-cancer effect of ZAA, relatively few studies have been conducted documenting the molecular mechanisms of ZAA inhibition of the growth of activated immune cells.…”

Apoptotic effects of a high performance liquid chromatography (HPLC) fraction of Antrodia camphorata mycelia are mediated by down-regulation of the expressions of four tumor-related genes in human non-small cell lung carcinoma A549 cell

“…The findings observed with the fermented broth of Antrodia camphorata indicated that the broth can evoke breast cancer cell apoptosis (Hseu et al, 2004(Hseu et al, , 2007(Hseu et al, , 2008Yang et al, 2006). The apoptotic studies conducted with the wild fruit bodies of Antrodia camphorata demonstrated that the ethanol extract of fruit body can induce HL-60 cell apoptosis partially through the hypoacetylation (Lu et al, 2009).…”