Oleifolioside B-mediated Autophagy Promotes Apoptosis in A549 Human Non-Small Cell Lung Cancer Cells

Int J Oncol. 2013 Dec;43(6):1943-50. doi: 10.3892/ijo.2013.2143. Epub 2013 Oct 17.

Abstract

The biochemical mechanisms of cell death by oleifolioside B (OB), a cycloartane-type triterpene glycoside isolated from Dendropanax morbifera Leveille, were investigated in A549 human lung carcinoma cells. Our data indicated that exposure to OB led to caspase activation and typical features of apoptosis; however, apoptotic cell death was not prevented by z-VAD-fmk, a pan-caspase inhibitor, demonstrating that OB-induced apoptosis was independent of caspase activation. Subsequently, we found that OB increased autophagy, as indicated by an increase in monodansylcadaverine fluorescent dye-labeled autophagosome formation and in the levels of the autophagic form of microtubule-associated protein 1 light chain 3 and Atg3, an autophagy-specific gene, which is associated with inhibiting phospho-nuclear factor erythroid 2-related factor 2 (Nrf2) expression. However, pretreatment with bafilomycin A1, an autophagy inhibitor, attenuated OB-induced apoptosis and dephosphorylation of Nrf2. The data suggest that OB-induced autophagy functions as a death mechanism in A549 cells and OB has potential as a novel anticancer agent capable of targeting apoptotic and autophagic cell death and the Nrf2 signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Chloromethyl Ketones / pharmacology
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Autophagy / drug effects*
  • Autophagy-Related Proteins
  • CASP8 and FADD-Like Apoptosis Regulating Protein / biosynthesis
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Caspase 3 / metabolism
  • Caspase 8 / metabolism
  • Caspase 9 / metabolism
  • Caspase Inhibitors / pharmacology
  • Cell Line, Tumor
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Inhibitor of Apoptosis Proteins / biosynthesis
  • Lung Neoplasms / drug therapy*
  • Macrolides / pharmacology
  • Microtubule-Associated Proteins / biosynthesis
  • Microtubule-Associated Proteins / metabolism
  • NF-E2-Related Factor 2 / biosynthesis
  • NF-E2-Related Factor 2 / metabolism
  • Plant Extracts / pharmacology
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Saponins / pharmacology*
  • Survivin
  • Ubiquitin-Conjugating Enzymes / biosynthesis
  • Ubiquitin-Conjugating Enzymes / metabolism

Substances

  • Amino Acid Chloromethyl Ketones
  • Antineoplastic Agents
  • Autophagy-Related Proteins
  • BIRC5 protein, human
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • Caspase Inhibitors
  • Enzyme Inhibitors
  • Inhibitor of Apoptosis Proteins
  • Macrolides
  • Microtubule-Associated Proteins
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Plant Extracts
  • Proto-Oncogene Proteins c-bcl-2
  • Saponins
  • Survivin
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
  • light chain 3, human
  • oleifolioside B
  • bafilomycin A1
  • Ubiquitin-Conjugating Enzymes
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • ATG3 protein, human