PMID- 33827387 OWN - NLM STAT- MEDLINE DCOM- 20210924 LR - 20210924 IS - 1793-6853 (Electronic) IS - 0192-415X (Linking) VI - 49 IP - 4 DP - 2021 TI - 4-Acetylantrocamol LT3 Inhibits Glioblastoma Cell Growth and Downregulates DNA Repair Enzyme O(6)-Methylguanine-DNA Methyltransferase. PG - 983-999 LID - 10.1142/S0192415X21500476 [doi] AB - Glioblastoma multiforme (GBM) is a deadly malignant brain tumor that is resistant to most clinical treatments. Novel therapeutic agents that are effective against GBM are required. Antrodia cinnamomea has shown antiproliferative effects in GBM cells. However, the exact mechanisms and bioactive components remain unclear. Thus, the present study aimed to investigate the effect and mechanism of 4-acetylantrocamol LT3 (4AALT3), a new ubiquinone from Antrodia cinnamomeamycelium, in vitro. U87 and U251 cell lines were treated with the indicated concentration of 4AALT3. Cell viability, cell colony-forming ability, migration, and the expression of proteins in well-known signaling pathways involved in the malignant properties of glioblastoma were then analyzed by CCK-8, colony formation, wound healing, and western blotting assays, respectively. We found that 4AALT3 significantly decreased cell viability, colony formation, and cell migration in both in vitro models. The epidermal growth factor receptor (EGFR), phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR), Hippo/yes-associated protein (YAP), and cAMP-response element binding protein (CREB) pathways were suppressed by 4AALT3. Moreover, 4AALT3 decreased the level of DNA repair enzyme O(6)-methylguanine-DNA methyltransferase and showed a synergistic effect with temozolomide. Our findings provide the basis for exploring the beneficial effect of 4AALT3 on GBM in vivo. FAU - Lee, Shih-Yu AU - Lee SY AD - Graduate Institute of Aerospace and Undersea Medicine, 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, Jang-Chun AU - Lin JC AD - Department of Radiation Oncology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan. AD - Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. FAU - Chung, Min-Chieh AU - Chung MC AD - Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei, Taiwan. FAU - Liu, Wei-Hsiu AU - Liu WH AD - Department of Surgery, School of Medicine, National Defense Medical Center, Taipei, Taiwan. AD - Department of Neurological Surgery Tri-Service General Hospital and National Defense Medical Center, No. 325, Sec. 2 Cheng-Kung Road Taipei 11490, Taiwan. LA - eng PT - Journal Article DEP - 20210406 PL - Singapore TA - Am J Chin Med JT - The American journal of Chinese medicine JID - 7901431 RN - 0 (Cyclohexanones) RN - 1339-63-5 (Ubiquinone) RN - 5Z93L87A1R (Guanine) RN - 72XZO87CZJ (4-acetylantroquinonol B) RN - 9B710FV2AE (O-(6)-methylguanine) RN - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferase 1) RN - EC 2.1.1.37 (DNMT1 protein, human) RN - OL659KIY4X (4-Butyrolactone) SB - IM MH - 4-Butyrolactone/*analogs & derivatives/chemistry/pharmacology MH - Cell Line, Tumor MH - Cell Movement/drug effects MH - Cell Survival/drug effects MH - Cyclohexanones/chemistry/*pharmacology MH - DNA (Cytosine-5-)-Methyltransferase 1/*metabolism MH - DNA Repair/*drug effects MH - Down-Regulation MH - Glioblastoma/*drug therapy MH - Guanine/*analogs & derivatives/metabolism MH - Humans MH - Ubiquinone/pharmacology OTO - NOTNLM OT - 4-Acetylantrocamol LT3 OT - CREB OT - Glioblastoma Multiforme OT - MGMT OT - YAP OT - mTOR EDAT- 2021/04/09 06:00 MHDA- 2021/09/25 06:00 CRDT- 2021/04/08 05:31 PHST- 2021/04/09 06:00 [pubmed] PHST- 2021/09/25 06:00 [medline] PHST- 2021/04/08 05:31 [entrez] AID - 10.1142/S0192415X21500476 [doi] PST - ppublish SO - Am J Chin Med. 2021;49(4):983-999. doi: 10.1142/S0192415X21500476. Epub 2021 Apr 6.