Lupalbigenin from Derris scandens Sensitizes Detachment-induced Cell Death in Human Lung Cancer Cells

Anticancer Res. 2015 May;35(5):2827-34.

Abstract

Background/aim: The ability of cancer cells to resist to anoikis has been shown to augment cancer cell metastasis in many cancers. In search for potential substances for anti-metastatic approaches, this study aimed to investigate anoikis-sensitizing activity of lupalbigenin, extracted from Derris scandens.

Materials and methods: Human lung cancer cells were treated with non-cytotoxic concentrations of lupalbigenin in a detachment condition. Anoikis was evaluated at various time points using MTT viability assays. The effect of lupalbigenin on anchorage-independent growth was performed by soft-agar assay. The survival signaling proteins, as well as regulatory proteins of apoptosis and metastasis, were examined by western blot analysis.

Results: Lupalbigenin treatment significantly down-regulated survival proteins, including protein kinase B (pAKT/AKT) and extracellular signal-regulated kinase (pERK/ERK), as well as anti-apoptotic protein B-cell lymphoma 2 (BCL-2), resulting in the enhancement of the cellular response to anoikis and the decrease of growth and survival in an anchorage-independent condition.

Conclusion: Lupalbigenin sensitizes detachment-induced cell death in human lung cancer cell through down-regulation of pro-survival proteins.

Keywords: Derris scandens; Lung cancer; anoikis; lupalbigenin; pro-survival pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anoikis / drug effects*
  • Apoptosis / drug effects
  • Apoptosis Regulatory Proteins / biosynthesis*
  • Apoptosis Regulatory Proteins / genetics
  • Cell Line, Tumor
  • Derris / chemistry
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Isoflavones / administration & dosage*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Mitogen-Activated Protein Kinases / biosynthesis
  • Neoplasm Metastasis
  • Plant Extracts / administration & dosage*
  • Plant Extracts / chemistry
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Signal Transduction / drug effects

Substances

  • Apoptosis Regulatory Proteins
  • Isoflavones
  • Plant Extracts
  • Proto-Oncogene Proteins c-bcl-2
  • lupalbigenin
  • Mitogen-Activated Protein Kinases