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Original Articles: Research

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

, , , , , , , , & show all
Pages 1085-1097 | Received 05 May 2010, Accepted 09 Jan 2011, Published online: 21 Mar 2011
 

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.

Acknowledgements

Support from the Purdue University Center for Cancer Research Small Grants Program is gratefully acknowledged. D.T.H. was supported by the NIH grant RCA128770A.

Potential conflict of interest:

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.

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