Using the gene expression signature of scutebarbalactone VN isolated from Scutellaria barbata to elucidate its anticancer activities

5^th Asia-Pacific Summit on Cancer Therapy

July 20-22, 2015 Brisbane, Australia

Do Thi Thao1, Chi-Ying Huang2, Kuan-TingLin2, Nguyen XuanCuong1, Nguyen Hoai Nam1 and Chau Van Minh1

Posters Accepted Abstracts: J Cancer Sci Ther

Abstract :

Bioassay-guided fractionation led to the discovery of a novel neo-clerodane diterpenoid, scutebarbalactone VN (BalA: 8, 13-epoxy-3-en-7-hydroxy-6, 11-O-dibenzoyl-15, 16-clerodanolide), from the whole-plant methanol extract of Vietnamese Scutellaria barbata D. Don. A microarray technique combined with bio-informatic analyses showed that BalA could inhibit cell cycle pathways by down regulating genes such as CDC25A and AURKA. BalA also showed the potential to reactivate down regulated genes in hepatocellular carcinoma cells and genes in antioxidant pathways such as HMOX1 and HSPA1A. Querying Connectivity map 2.0 resulted in a match of the BalA-modulated gene signature with that of the 10 known compounds, most of which are currently marketed chemotherapy drugs. The highest matching scores belonged to lomustine, semustine, and withaferin A. Lomustine and semustine were found to alkylate DNA and RNA molecules, while withaferin A inhibits nuclear factor kappa B (NF-κB) activity. A luciferase reporter assay was also conducted on 293/NF-κB human embryonic kidney cells that had been transfected with the NF-κB-luciferase plasmid to verify the anticancer activity of BalA. The assay showed that Ba1A effectively blocked NF-κB with an IC50 of 38.60±0.05 μM.