The natural products parthenolide and andrographolide exhibit anti-cancer stem cell activity in multiple myeloma.

Abstract

Multiple myeloma (MM) is an incurable plasma cell malignancy where nearly all patients succumb to a relapse. The current preclinical models of MM target the plasma cells, constituting the bulk of the tumor, leaving the cancer stem cells to trigger a relapse. Utilizing a three-dimensional tissue culture system where cells were grown in extracellular matrix designed to reconstruct human bone marrow, we tested the anti-multiple myeloma cancer stem cell (MM-CSC) potential of two natural product inhibitors of nuclear factor κB (NFκB). Here we show that parthenolide and andrographolide are potent anti-MM-CSC agents. Both natural products demonstrated preferential toxicity toward MM-CSCs over non-tumorigenic MM cells. Addition of the bone marrow stromal compartment abrogated andrographolide activity while having no effect on parthenolide cytoxicity. This is the first report of a natural product with anti-CSC activity in myeloma, suggesting that it has the potential to improve the survival of patients with MM by eliminating the relapse-causing MM-CSCs.

Authors

Gunn, Ellen J; Williams, John T; Huynh, Daniel T; Iannotti, Mike; Han, Changho; Barrios, Francis J; Kendall, Stephen; Glackin, Carlotta A; Colby, David A; Kirshner, Julia;

Keywords

  • Andrographis/ chemistry
  • Anti-Inflammatory Agents, Non-Steroidal/ pharmacology
  • Antineoplastic Agents/ pharmacology
  • Apoptosis/ drug effects
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cell Proliferation/ drug effects
  • Cell Survival/ drug effects
  • Diterpenes/ chemistry
  • Diterpenes/ pharmacology
  • Dose-Response Relationship, Drug
  • Humans
  • Molecular Structure
  • Multiple Myeloma/ drug therapy
  • Multiple Myeloma/ metabolism
  • Multiple Myeloma/ pathology
  • NF-kappa B/ antagonists & inhibitors
  • Neoplastic Stem Cells/ drug effects
  • Neoplastic Stem Cells/ metabolism
  • Neoplastic Stem Cells/ pathology
  • Plant Extracts/ chemistry
  • Plant Extracts/ pharmacology
  • Sesquiterpenes/ chemistry
  • Sesquiterpenes/ pharmacology
  • Tanacetum parthenium/ chemistry

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