High-elevation cultivation increases anti-cancer podophyllotoxin accumulation in Podophyllum hexandrum

Podophyllum hexandrum, a perennial alpine herb produces the anti-cancer metabolite podophyllotoxin (PPT) that is in large part responsible for the plant's endangered species status. Since PPT commercial production via chemical synthesis, biotechnological intervention and/or cultivation by ex situ conditions have yet to meet the ever-increasing demand for this potent anticancer drug, identifying cultivation practices to improve PPT accumulation is essential. While P. hexandum is indigenous to the mountainous Himalayan region of Asia, effect of elevations on plant growth and PPT accumulation has not been systematically investigated. Here is reported plant growth and PPT production at two elevations: 2300 and 3300 m. To dissect genetic versus environmental conditions responsible for enhanced growth at the higher elevation, plants adapted to each elevation were transplanted to the alternative site. Aerial and rhizome dry-weight was 1.4- to 2.0-fold and 1.2- to 2.0-fold greater, respectively at the 3300 m versus the 2300-m site for 3- to 5-year-old plants. Other growth parameters including leaf area, rhizome length/diameter, number of petioles, root and fruit per plant and fruit dry weight per plant showed an increased value at the higher elevation. PPT content in the aerial portions and rhizomes for all years studied was greater at the 3300 m with 2.2- to 5.3-fold and 2.2- to 3.5-fold on a per plant basis compared to the 2300-m site. Based on the plant's perennial and fruiting characteristics, a sustainable harvesting scheme that includes the plant's aerial portions, rhizomes and seeds is proposed for improving PPT yield without over harvesting of this endangered species.