Frondoside A from sea cucumber and nymphaeols from Okinawa propolis: Natural anti-cancer agents that selectively inhibit PAK1 in vitro

Drug Discov Ther. 2017 May 30;11(2):110-114. doi: 10.5582/ddt.2017.01011. Epub 2017 Apr 24.


A sulfated saponin called "Frondoside A" (FRA) from sea cucumber and ingredients from Okinawa propolis (OP) have been previously shown to suppress the PAK1-dependent growth of A549 lung cancer as well as pancreatic cancer cells. However, the precise molecular mechanism underlying their anti-cancer action still remains to be clarified. In this study, for the first time, we found that both FRA and OP directly inhibit PAK1 in vitro in a selective manner (far more effectively than two other oncogenic kinases, LIMK and AKT). Furthermore, at least two major anti-cancer ingredients of OP, nymphaeols A and C, also directly inhibit PAK1 in vitro in a selective manner. To the best of our knowledge, FRA is the first marine compound that selectively inhibits PAK1. Likewise, these nymphaeols are the first propolis ingredients that selectively inhibit PAK1.

Keywords: PAK1; Propolis; cancers; frondoside A; nymphaeols; sea cucumber.

MeSH terms

  • A549 Cells
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Chromatography, High Pressure Liquid
  • Flavanones / chemistry
  • Flavanones / pharmacology
  • Flavonoids / chemistry
  • Flavonoids / pharmacology
  • Glycosides / chemistry
  • Glycosides / pharmacology*
  • Humans
  • In Vitro Techniques
  • Lim Kinases / antagonists & inhibitors
  • Lim Kinases / drug effects
  • Propolis / chemistry
  • Propolis / pharmacology*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / drug effects
  • Sea Cucumbers
  • Triterpenes / chemistry
  • Triterpenes / pharmacology*
  • p21-Activated Kinases / antagonists & inhibitors
  • p21-Activated Kinases / drug effects*


  • Antineoplastic Agents
  • Flavanones
  • Flavonoids
  • Glycosides
  • Triterpenes
  • frondoside A
  • nymphaeol C
  • propolin C
  • Propolis
  • LIMK1 protein, human
  • Lim Kinases
  • PAK1 protein, human
  • Proto-Oncogene Proteins c-akt
  • p21-Activated Kinases