Eburicoic Acid, an Active Triterpenoid from the Fruiting Bodies of Basswood Cultivated Antrodia cinnamomea, Induces ER Stress-Mediated Autophagy in Human Hepatoma Cells

Abstract

Antrodia cinnamomea, a Taiwan-specific medicinal mushroom, can manipulate biological activities, including hepatoprotection, anti-inflammation, anti-hepatitis B virus activity, anticancer activity, etc. In this study, the anti-liver cancer activity and molecular mechanisms of eburicoic acid, the second most abundant triterpenoid from the fruiting bodies of basswood cultivated Antrodia cinnamomea was investigated using the human hepatoma Hep 3B cells. The results show that eburicoic acid effectively reduced Hep 3B cell viability within 24 hours, and the IC50 was 18.4 μM, which was equivalent to 8.7 μg/mL. Besides, eburicoic acid induced conversion of LC3-I to LC3-II and a large number of autophagosomes/autolysosomes formation. In depth investigation for the molecular mechanisms, revealed that eburicoic acid firstly promoted reactive oxygen species generation and ATP depletion, leading to endoplasmic reticulum stress, followed by elevated cytosolic calcium ion concentration and BiP expression, downregulated phosphorylation of DAPK, upregulated phosphorylation of Beclin-1, JNK, and Bcl-2, and finally induced autophagy in Hep 3B cells. These results indicate that eburicoic acid has significant anti-liver cancer effects and more distinctive mechanisms.