Arthpyrone L, a New Pyridone Alkaloid from a Deep-Sea Arthrinium sp., Inhibits Proliferation of MG63 Osteosarcoma Cells by Inducing G0/G1 Arrest and Apoptosis

Chem Biodivers. 2021 Feb;18(2):e2000639. doi: 10.1002/cbdv.202000639. Epub 2021 Feb 3.

Abstract

Fractionation of the ethanol extract of a marine fungus, Arthrinium sp., afforded a new pyridone alkaloid (arthpyrone L (1)), the structure with absolute configuration of which was established by comprehensive spectroscopic analyses. In vitro cell viability assays revealed that compound 1 showed antiproliferative effects toward human A549 (lung), MG63, U2OS (bone), MCF-7 and MDA-MB-231 (breast) cancer cells. MG63 cell lines were chosen for further biological evaluations and presented apoptosis and cell cycle arrest (G0/G1 phase) upon treatment of 1. Subsequent mechanism studies demonstrated that the growth inhibition of 1 against MG63 cells was via activation of caspase-modulated apoptotic pathway and inhibition of PI3K/Akt pathway.

Keywords: Arthrinium; antiproliferation; arthpyrone L; osteosarcoma.

MeSH terms

  • Alkaloids / chemistry
  • Alkaloids / pharmacology
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Ascomycota / chemistry*
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / metabolism
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • G1 Phase / drug effects
  • Humans
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / metabolism
  • Pyridones / chemistry
  • Pyridones / pharmacology*

Substances

  • Alkaloids
  • Antineoplastic Agents
  • Pyridones
  • arthpyrone A