Using the Gene Expression Signature of Scutebarbalactone VN Isolated from Scutellaria barbata to Elucidate its Anticancer Activities

作者：Do Thi Thao^*; Huang Chi Ying; Lin Kuan Ting; Do Thi Phuong; Nguyen Thi Nga; Nguyen Thi Trang; Nguyen Thi Cue; Nguyen Xuan Cuong; Nguyen Hoai Nam; Chau Van Minh

来源：Natural Product Communications, 2015, 10(2): 353-355.

DOI：10.1177/1934578x1501000237

• Scutellaria barbata
• Scutebarbalactone VN
• AURKA
• BaIA
• CDC25A
• COX-2
• Microarray
• Neo-clerodane
• NF-kappa B

Bioassay-guided fractionation led to the discovery of a novel rieo-clerodane diterpenoid, scutebarbalactone VN (Ba1A: 8,13-epoxy-3-en-7-hydroxy-6,11-O-dibenzoyl-15,16-clerodanolide), from the methanol extract of the whole-plant of Vietnamese Scutellaria barbata D. Don. A microarray technique combined with bioinformatic analyses showed that Ba1A could inhibit cell cycle pathways by downregulating genes such as CDC25A and AURKA. Ba1A also showed the potential to reactivate downregulated 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 Ba1A-modulated gene signature with that of 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, while withaferin A inhibits nuclear factor kappa B (NF-kappa B) activity. A luciferase reporter assay was also conducted on 293/NF-kappa B human embryonic kidney cells that had been transfected with the NF-kappa B-luciferase plasmid to verify the anticancer activity of Ba1A. The assay showed that Ba1A effectively blocked NF-kappa B with an IC50 of 38.6 +/- 0.05 mu M.

• 出版日期2015-2