Diterpenoids from Scutellaria barbata induce tumour-selective cytotoxicity by taking the brakes off apoptosis

Abstract

Medicinal plants are an excellent source of structurally diverse, bio-active compounds with potential in the fight against cancer. One of the most promising is Scutellaria barbata, prescribed traditionally for the treatment of cancers. Scutebarbatine A is the major diterpenoid, produced in specialized large, peltate trichomes on leaves of S. barbata. It induces dose-dependent apoptosis, specifically in cancer cells. The major class of proteins down-regulated are pro-survival proteins, the Inhibitors of Apoptosis (IAPs), and IAP regulating proteins. We propose that scutebarbatine A works by releasing the molecular brakes (the IAPs) on apoptosis in cell death-evading cancer cells. Comparison between the cytotoxicity of methanolic extracts of S. barbata leaves and decoctions (Ban Zhi Lian) prepared traditionally, showed substantially different chemical compositions and differential induction of apoptosis. Analyses suggest polyvalency between the constituents in both extracts, and ways to produce enhanced chemopreventive preparations for the treatment of cancer.

Keywords

• scutellaria barbata
• clerodane diterpenoids
• traditional chinese medicine
• apoptosis
• cancer
• inhibitors of apoptosis
• iaps