Alpha-terpineol affects synthesis and antitumor activity of triterpenoids from Antrodia cinnamomea mycelia in solid-state culture.

To enhance production of Antrodia cinnamomea triterpenoids (ACTs) from mycelia in solid-state culture, α-terpineol was added to the medium as an elicitor at an optimal concentration of 0.05 mL L-1. Multi-stage solvent extraction and HPLC analysis were performed, and the compositions of ACTs-E (from culture with elicitor) and ACTs-NE (from culture without elicitor) were found to be quite different. In assays of in vitro antitumor activity, ACTs-E, in comparison with ACTs-NE, produced stronger viability reduction in several tumor cell lines and stronger apoptosis induction in HeLa in a dose-dependent manner. Several related proteins involved in the mitochondrial pathway of apoptosis (p53, Bax, caspase-3) did not show expression upregulation by ACTs-E, suggesting that apoptosis induction occurred through a p53-independent process. Further analysis revealed that ACTs-E strongly inhibited synthesis of topoisomerase I (TOP1) and tyrosyl-DNA phosphodiesterase I (TDP1), which are involved in DNA repair, at both transcriptional and protein levels. Our findings suggest that ACTs-E have potential for applications in the pharmaceutical, clinical, and functional food industries, as a novel antitumor agent and a dual TOP1/TDP1 inhibitor.

A polysaccharide from Antrodia cinnamomea mycelia exerts antitumor activity through blocking of TOP1/TDP1-mediated DNA repair pathway.

A polysaccharide (termed ACPS-1) from mycelia of Antrodia cinnamomea under submerged culture was purified by hot water extraction and successive DEAE-52 cellulose and Sephadex G-100 column chromatography, and structurally characterized by FTIR, NMR, periodate oxidation, Smith degradation, and GC-MS. ACPS-1 (MW 2.296 × 104 Da) was composed primarily of Man, Xyl, Ara, Fuc and Rha with a molar ratio of 31.27:1.77:1.44:1.34:1.00, and its backbone consisted of repeating α-(1 → 3), α-(1 → 6), α-(1 → 2), and α-(1 → 4) glycosidic linkages. ACPS-1 displayed strong in vitro growth-inhibitory effects on several human and mouse cancer cell lines (HeLa, A431, H22 and S180), and were not cytotoxic to normal mouse spleen cells. Studies of the inhibitory mechanism revealed that ACPS-1 induced apoptosis and cell cycle arrest (cells remained in G2/M phase) through blocking of topoisomerase I/tyrosyl-DNA phosphodiesterase I (TOP1/TDP1)-mediated DNA repair pathway. Our findings suggest that ACPS-1 has strong potential applications in pharmaceutical and food industries, and as a novel anticancer agent based on its dual TOP1/TDP1 inhibitory effect.