4-acetylantroquinonol-b and Liver-Neoplasms

The functions of 4-acetylantroquinonol B (4-AAQB), a ubiquinone derivative isolated from the mycelium of Antrodia cinnamomea, in immunotherapy for liver cancer were investigated. We found that 4-AAQB could inhibit liver cancer stem cell related manifestations and activate the antitumor ability of dendritic cells. Specifically, 4-AAQB can inhibit EpCAM, AFP and related pathways of HepG2 cells. It also significantly decreases the expression of β-catenin, inhibits the tumorigenicity and decreases the secretion of immune escape related cytokines. Moreover, 4-AAQB can stimulate the proliferation of immune cells and promote the endocytosis of immature dendritic cells. When co-cultured immature dendritic cells with EpCAM+ HepG2 cells, 4-AAQB enhanced the expression of MHC class I and II on the surface of liver cancer stem cells and dendritic cells, increased the expression of costimulatory molecules CD80 of dendritic cells and cytokines related to immune activation. In conclusion, 4-AAQB from Antrodia cinnamomea can enhance immune function of dendritic cells against liver cancer stem cells, and may have the potential to be used for liver cancer prevention and immunotherapy.

Topics: 4-Butyrolactone; Animals; Antrodia; Cell Survival; Coculture Techniques; Cyclohexanones; Dendritic Cells; Dose-Response Relationship, Drug; Hep G2 Cells; Humans; Immunity, Cellular; Liver Neoplasms; Mice; Neoplastic Stem Cells; RAW 264.7 Cells

Hepatocellular carcinoma (HCC) has become one of most common malignancies and a leading cause of cancer mortality worldwide. Previous study has shown that 4-acetylantroquinonol B (4AAQB) isolated from Antrodia cinnamomea (or niu-chang-chih) was observed to inhibit HepG2 cell proliferation via affecting cell cycle. However, the in vivo effects and antimetastatic activity of 4AAQB have not yet been addressed. This study found that 4AAQB inhibited HepG2 and HuH-7 hepatoma cell growth in both in vitro and in vivo models and exhibited pronounced inhibitory effects on HuH-7 tumor growth in xenograft and orthotopic models. 4AAQB efficiently inhibited the phosphorylation of mTOR and its upstream kinases and the downstream effectors and decreased the production of VEGF and activity of Rho GTPases in HuH-7 cells. Furthermore, 4AAQB inhibited in vitro HuH-7 cell migration and in vivo pulmonary metastasis. The results suggested that 4AAQB is a potential candidate for HCC therapy.

Topics: 4-Butyrolactone; Animals; Antineoplastic Agents; Antrodia; Carcinoma, Hepatocellular; Cell Movement; Cell Proliferation; Cyclohexanones; Down-Regulation; Hep G2 Cells; Humans; Liver Neoplasms; Male; Metatarsal Bones; Mice, Nude; Mice, SCID; Phosphorylation; Protein Biosynthesis; Signal Transduction; TOR Serine-Threonine Kinases; Vascular Endothelial Growth Factor A

Antrodia cinnamomea is known for its antihepatoma activity, yet the identity of its active compound was unclear. In this study, a 5-ton fermenter was used to prepare sufficient mycelium of A. cinnamomea for active compound isolation and identification.. Using antiproliferative activity toward HepG2 cells as guidance in the isolation process, 4-acetylantroquinonol B was purified and identified to be the major bioactive compound of A. cinnamomea cultivated by submerged fermentation. The median effective doses (EC(50)) of 4-acetylantroquinonol B for HepG2 cells were 0.10 +/- 0.00 and 0.08 +/- 0.00 microg mL(-1) for 72 and 96 h treatments, respectively. The selective indices of 4-acetylantroquinonol B were 100 and 125 for 72 and 96 h treatments, respectively, indicating that this compound had high selective activity for hepatoma cells.. 4-Acetylantroquinonol B is the major antihepatoma constituent of Antrodia cinnamomea mycelium produced by submerged fermentation.

Topics: 4-Butyrolactone; Antineoplastic Agents; Antrodia; Biological Products; Carcinoma, Hepatocellular; Cell Proliferation; Cyclohexanones; Fermentation; Hep G2 Cells; Humans; Liver Neoplasms; Mycelium