Antroquinonol Targets FAK-Signaling Pathway Suppressed Cell Migration, Invasion, and Tumor Growth of C6 Glioma

• Published in: PloS one Vol. 10; no. 10; p. e0141285
• Main Authors: Thiyagarajan, Varadharajan, Tsai, May-Jywan, Weng, Ching-Feng
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.10.2015; Public Library of Science (PLoS)
• Subjects: Adhesive bonding; Analysis; Animals; Antibiotics; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Atomic force microscopy; Biotechnology; Brain tumors; Care and treatment; Cdc42 protein; Cell adhesion & migration; Cell cycle; Cell Line, Tumor; Cell migration; Cell morphology; Cell Movement - drug effects; Cell Proliferation - drug effects; Cell survival; Cell Survival - drug effects; Cellular signal transduction; Complications and side effects; Cytochrome; Cytology; Focal adhesion kinase; Focal Adhesion Kinase 1 - metabolism; G1 phase; Gene Expression Regulation, Neoplastic - drug effects; Glioma; Glioma - drug therapy; Glioma - enzymology; Glioma cells; Gliomas; Immunoglobulins; Kinases; Life sciences; Liver cancer; Lung cancer; Mesenchyme; Metastases; Metastasis; Mice; Microscopy; Molecular docking; Molecular Docking Simulation; Motility; Neoplasm Invasiveness; Neuroblastoma; p53 Protein; Phosphorylation; Proteins; Rac1 protein; Rats; Signal transduction; Signal Transduction - drug effects; Signaling; Streptococcus infections; Tumorigenesis; Tumors; Tyrosine; Ubiquinone - administration & dosage; Ubiquinone - analogs & derivatives; Ubiquinone - chemistry; Ubiquinone - pharmacology; Xenograft Model Antitumor Assays; Xenografts; Xenotransplantation; Taiwan; United Kingdom > UK; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0141285

Focal adhesion kinase (FAK) is a non-receptor protein tyrosine that is overexpressed in many types of tumors and plays a pivotal role in multiple cell signaling pathways involved in cell survival, migration, and proliferation. This study attempts to determine the effect of synthesized antroquinonol on the modulation of FAK signaling pathways and explore their underlying mechanisms. Antroquinonol significantly inhibits cell viability with an MTT assay in both N18 neuroblastoma and C6 glioma cell lines, which exhibits sub G1 phase cell cycle, and further induction of apoptosis is confirmed by a TUNEL assay. Antroquinonol decreases anti-apoptotic proteins, whereas it increases p53 and pro-apoptotic proteins. Alterations of cell morphology are observed after treatment by atomic force microscopy. Molecular docking results reveal that antroquinonol has an H-bond with the Arg 86 residue of FAK. The protein levels of Src, pSrc, FAK, pFAK, Rac1, and cdc42 are decreased after antroquinonol treatment. Additionally, antroquinonol also regulates the expression of epithelial to mesenchymal transition (EMT) proteins. Furthermore, antroquinonol suppresses the C6 glioma growth in xenograft studies. Together, these results suggest that antroquinonol is a potential anti-tumorigenesis and anti-metastasis inhibitor of FAK.