A new anti-austerity agent, 4'-O-methylgrynullarin from Derris scandens induces PANC-1 human pancreatic cancer cell death under nutrition starvation via inhibition of Akt/mTOR pathway

Bioorg Med Chem Lett. 2021 May 15:40:127967. doi: 10.1016/j.bmcl.2021.127967. Epub 2021 Mar 19.

Abstract

An ethanolic extract of Derris scandens flowers showed potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrient-deprived condition, with a PC50 value of 0.7 μg/mL. Phytochemical investigation of this active extract led to the isolation of four prenylated isoflavones (1-4) including a new compound named 4'-O-methylgrynullarin (1). The structure elucidation of the new compound was achieved by HRFABMS and NMR spectroscopic analysis. The isolated compounds exhibited potent anti-austerity activity against four different human pancreatic cancer cell lines under nutrient-deprived conditions. The new compound 4'-O-methylgrynullarin (1) was also found to inhibit PANC-1 cell migration and colony formation under nutrient-rich condition. Mechanistically, compound 1 inhibited key survival proteins in the Akt/mTOR signaling pathway. Therefore, 4'-O-methylgrynullarin (1) can be considered as a potential lead compound for the anticancer drug development based on the anti-austerity strategy.

Keywords: Anti-austerity agents; Derris scandens; PANC-1; Pancreatic cancer; Preferential cytotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Death / drug effects*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Derris / chemistry
  • Drug Screening Assays, Antitumor
  • Flowers / chemistry
  • Hemiterpenes / chemical synthesis
  • Hemiterpenes / isolation & purification
  • Hemiterpenes / pharmacology*
  • Humans
  • Isoflavones / chemistry
  • Isoflavones / isolation & purification
  • Isoflavones / pharmacology*
  • Pancreatic Neoplasms / drug therapy*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects*
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • Hemiterpenes
  • Isoflavones
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases