Secalonic acid D induced leukemia cell apoptosis and cell cycle arrest of G(1) with involvement of GSK-3beta/beta-catenin/c-Myc pathway

Cell Cycle. 2009 Aug;8(15):2444-50. doi: 10.4161/cc.8.15.9170. Epub 2009 Aug 3.

Abstract

The anticancer activities of secalonic acid D separated from the secondary metabolites of the mangrove endophytic fungus No. ZSU44 were investigated in this study. Secalonic acid D showed potent cytotoxicity to HL60 and K562 cells, and the IC(50) values were 0.38 and 0.43 mumol/L, respectively. Annexin V-FITC/PI assay and western blot indicated that secalonic acid D induced apoptosis in HL60 and K562 cells. In addition, secalonic acid D led to cell cycle arrest of G(1) phase related to downregulation of c-Myc. Moreover, our data indicated that downregulation of c-Myc and cell cycle arrest of G(1) phase were caused not by formation of G-quadruplex structures but by activation of GSK-3beta followed by degradation of beta-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • G1 Phase / drug effects
  • G1 Phase / physiology
  • Glycogen Synthase Kinase 3 / drug effects
  • Glycogen Synthase Kinase 3 / metabolism*
  • Glycogen Synthase Kinase 3 beta
  • HL-60 Cells
  • Humans
  • Proto-Oncogene Proteins c-myc / antagonists & inhibitors
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • RNA, Small Interfering / metabolism
  • Xanthones / pharmacology*
  • Xanthones / toxicity
  • beta Catenin / antagonists & inhibitors
  • beta Catenin / metabolism*

Substances

  • Antineoplastic Agents
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • RNA, Small Interfering
  • Xanthones
  • beta Catenin
  • secalonic acid
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3