PMID- 32668963 OWN - NLM STAT- MEDLINE DCOM- 20201020 LR - 20211204 IS - 1793-6853 (Electronic) IS - 0192-415X (Linking) VI - 48 IP - 5 DP - 2020 TI - 4-Acetylantrocamol LT3, a New Ubiquinone from Antrodia cinnamomea, Inhibits Hepatocellular Carcinoma HepG2 Cell Growth by Targeting YAP/TAZ, mTOR, and WNT/beta-Catenin Signaling. PG - 1243-1261 LID - 10.1142/S0192415X20500615 [doi] AB - 4-acetylantrocamol LT3 (4AALT3), a new ubiquinone from the mycelium of Antrodia cinnamomea (Polyporaceae), has been recently shown to possess anticancer activity. However, the detailed mechanisms of such action remain unclear. In this study, the molecular mechanisms of 4AALT3 on hepatocellular carcinoma cells (HCC) were investigated. Human hepatocellular carcinoma cell line HepG2 cells were treated with concentrations of 4AALT3. Cell viability, colony formation, and the underlying mechanisms were then analyzed by CCK-8, colony formation, qPCR, and Western blotting assays. We found that 4AALT3 significantly decreased cell viability and colony formation in a dose-dependent manner. Accordingly, 4AALT3 significantly decreased protein levels of cyclin B, E1, D1, and D3, thereby facilitating cell cycle arrest. In addition, 4AALT3 significantly suppressed the nuclear localization of Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ), mammalian target of rapamycin (mTOR), and WNT/[Formula: see text]-catenin signaling pathways, all of which are well-known signaling pathways that contribute to the malignant properties of HCC. These effects are associated with activation of 5' AMP-activated protein kinase (AMPK) and autophagy. Our findings indicate that 4AALT3 exerts inhibitory effects on HepG2 cell growth via multiple signaling pathways and may be a potential agent for HCC therapy. FAU - Chen, Yen-Lin AU - Chen YL AD - Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan. AD - Department of Radiology, Taoyuan Armed Forces General Hospital, National Defense Medical Center, Taipei, Taiwan. FAU - Yen, I-Chuan AU - Yen IC AD - School of Pharmacy, National Defense Medical Center, Taipei, Taiwan. FAU - Lin, Kuen-Tze AU - Lin KT AD - Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan. AD - Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. FAU - Lai, Feng-Yi AU - Lai FY AD - Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei, Taiwan. FAU - Lee, Shih-Yu AU - Lee SY AD - Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan. AD - Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei, Taiwan. LA - eng PT - Journal Article PL - Singapore TA - Am J Chin Med JT - The American journal of Chinese medicine JID - 7901431 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Antineoplastic Agents, Phytogenic) RN - 0 (Transcription Factors) RN - 0 (Wnt Proteins) RN - 0 (YAP-Signaling Proteins) RN - 0 (YAP1 protein, human) RN - 0 (antrocamol) RN - 0 (beta Catenin) RN - 1339-63-5 (Ubiquinone) RN - EC 2.3.- (Acyltransferases) RN - EC 2.3.1.- (TAFAZZIN protein, human) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Acyltransferases MH - Adaptor Proteins, Signal Transducing/*metabolism MH - Antineoplastic Agents, Phytogenic MH - Antrodia/*chemistry MH - Autophagy/drug effects/genetics MH - Carcinoma, Hepatocellular/*genetics/*pathology MH - Hep G2 Cells MH - Humans MH - Liver Neoplasms/*genetics/*pathology MH - Signal Transduction/*drug effects MH - TOR Serine-Threonine Kinases/*metabolism MH - Transcription Factors/*metabolism MH - Ubiquinone/*analogs & derivatives/isolation & purification/*pharmacology MH - Wnt Proteins/*metabolism MH - YAP-Signaling Proteins MH - beta Catenin/*metabolism OTO - NOTNLM OT - 4-Acetylantrocamol LT3 OT - Autophagy OT - Hepatocellular Carcinoma Cells OT - Wnt/[Formula: see text]-Catenin, mTOR OT - YAP/TAZ EDAT- 2020/07/17 06:00 MHDA- 2020/10/21 06:00 CRDT- 2020/07/17 06:00 PHST- 2020/07/17 06:00 [entrez] PHST- 2020/07/17 06:00 [pubmed] PHST- 2020/10/21 06:00 [medline] AID - 10.1142/S0192415X20500615 [doi] PST - ppublish SO - Am J Chin Med. 2020;48(5):1243-1261. doi: 10.1142/S0192415X20500615.