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Withaferin A induces cell death and differentiation in multiple myeloma cancer stem cells

Mark E Issa1, Muriel Cuendet1

  • 1School of Pharmaceutical Sciences , University of Geneva , University of Lausanne , Rue Michel Servet 1 , CH-1211 Geneva 4 , Switzerland . Email: Muriel.Cuendet@unige.ch ; ; Tel: +41 22 379 3386.

Medchemcomm
|August 16, 2018
PubMed

Insights

Withaferin A (WFA) shows promise in treating multiple myeloma (MM) by inhibiting cancer stem cell (CSC) growth and promoting differentiation. Further research in animal models is recommended.

Area of Science:

  • Oncology
  • Cancer Stem Cell Biology
  • Pharmacology

Background:

  • Multiple myeloma (MM) is an incurable blood cancer.
  • Chemotherapy-resistant cancer stem cells (CSCs) contribute to MM persistence.
  • Differentiation therapy is a strategy to reduce CSC stemness.

Purpose of the Study:

  • To investigate the anticancer effects of withaferin A (WFA) on MM CSCs and MM plasma cells.
  • To evaluate WFA's impact on CSC stemness and differentiation markers.

Main Methods:

  • In vitro study of WFA on MM-CSCs and RPMI 8226 MM cells.
  • Assessed growth inhibition (IC50), cell cycle arrest, apoptosis, and cell morphology.
  • Utilized qPCR for gene expression analysis of stemness and differentiation markers.

Main Results:

  • WFA inhibited growth in both MM-CSCs (IC50=649 nM) and RPMIs (IC50=224 nM).
  • WFA induced G2 cell cycle arrest, cell death, and apoptosis.
  • WFA reduced stemness markers and promoted differentiation markers in MM-CSCs, with notable morphological changes.

Conclusions:

  • Withaferin A demonstrates significant anticancer activity against multiple myeloma cancer stem cells.
  • WFA reduces stemness and promotes differentiation in MM-CSCs, suggesting therapeutic potential.
  • Further investigation in MM animal models is warranted to explore WFA's efficacy.

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