Anti-cancer effect of betulin on a human lung cancer cell line: A pharmacoproteomic approach using 2 D SDS PAGE coupled with nano-HPLC tandem mass spectrometry

Sung Pyo Jae, Hun Roh Si, Ki Kim Dae, Gyun Lee Jin, Yook Lee Yong, Sun Hong Soon, Won Kwon Sung, Hill Park Jeong

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Betulin is a representative compound of Betula platyphylla, a tree species belonging to the Betulaceae family. In this investigation, we revealed that betulin showed anticancer activity on human lung cancer A549 cells by inducing apoptosis and changes in protein expression profiles were observed. Upon flow cytometry analysis, the surface of betulin-treated cells was found to be annexin-V positive and propidium iodide (PI) negative, which indicated that the cells were apoptotic. In order to identify the molecular players involved in betulin-induced apoptosis, cellular proteins were applied to two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (2 D SDS PAGE) for differential proteomic analysis. As a result, four downregulated proteins and three upregulated proteins were identified by nano-HPLC MS/MS. The four downregulated proteins were poly(rC)-binding protein 1, isoform 1 of 3-hydroxyacyl-CoA dehydrogenase type 2, heat shock protein 90-alpha 2, and enoyl-CoA hydratase; the three upregulated proteins were aconitate hydratase, malate dehydrogenase, and splicing factor arginine/serine-rich 1. These differentially expressed proteins explained the cytotoxicity of betulin against human lung cancer A549 cells, and the proteomic approach was thus shown to be a potential tool for understanding the pharmacological activities of pharmacophores.

Original languageEnglish (US)
Pages (from-to)127-131
Number of pages5
JournalPlanta Medica
Volume75
Issue number2
DOIs
StatePublished - Feb 1 2009

Keywords

  • A549 cell line
  • Betula platyphylla
  • Betulaceae
  • Betulin
  • Nano-HPLC MS/MS
  • Proteomics

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

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