Using the gene expression signature of scutebarbalactone VN isolated from Scutellaria barbata to elucidate its anticancer activities.
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 methanol extract of the whole-plant of Vietnamese Scutellaria barbata D. Don. A microarray technique combined with bioinformatic analyses showed that BalA could inhibit cell cycle pathways by downregulating genes such as CDC25A and AURKA. BalA 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 BalA-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-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 BalA effectively blocked NF-κB with an IC50 of 38.6 ± 0.05 μM.
Do Thi
do T
Thao
Chi-Ying
CY
Huang
Kuan-Ting
KT
Lin
Do Thi
do T
Phuong
Nguyen Thi
NT
Nga
Nguyen Thi
NT
Trang
Nguyen Thi
NT
Cuc
Nguyen Xuan
NX
Cuong
Nguyen Hoai
NH
Nam
Chau Van
CV
Minh
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000494:pharmacology*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D040081:Protein Array Analysis; D031363:Scutellaria / Q000737:chemistry*; D015854:Up-Regulation
D000972:Antineoplastic Agents, Phytogenic