Induction of Benzo[c]phenanthridine Alkaloid Biosynthesis in Suspension Cell Cultures ofSanguinaria canadensisby Retinoic Acid Derivatives

Abstract

Abstract Treatment of suspension-cell cultures of Sanguinaria canadensis L. (SCP-GM) with a series of natural and synthetic retinoic acid derivatives induced benzophenanthridine alkaloid biosynthesis in a dose-dependent manner. Suspension cells were treated with one of the following: retinoic acid (RA), retinol (ROH), retinal (RHO). 13- cis-retinoic acid (cis-RA), or retinyl acetate (ROAc) in concentrations ranging from 1 to 50 μM (24 h). Each of the RA derivatives tested increased the cellular alkaloid concentrations of sanguinarine and chelerythrine by 97 to 470% (approximately 0.045–0.23% dry wt) depending on the reinoid and the dosage employed. Control SCP-GM suspension-cells accumulated only trace amounts of sanguinarine and chelerythrine, approximately 0.005% dry wt and 0.004% dry wt, respectively. The activity of S-adenosyl methionine: tetrahydroberberine-.V-methyltransferase, a key branch point enzyme in the benzophenanthridine biosynthetic pathway, was also induced over 24 h after treatment of th...