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Targeting breast stem cells with the cancer preventive compounds curcumin and piperine

Breast Cancer Research and Treatment volume 122, pages 777–785 (2010)Cite this article

Abstract

The cancer stem cell hypothesis asserts that malignancies arise in tissue stem and/or progenitor cells through the dysregulation or acquisition of self-renewal. In order to determine whether the dietary polyphenols, curcumin, and piperine are able to modulate the self-renewal of normal and malignant breast stem cells, we examined the effects of these compounds on mammosphere formation, expression of the breast stem cell marker aldehyde dehydrogenase (ALDH), and Wnt signaling. Mammosphere formation assays were performed after curcumin, piperine, and control treatment in unsorted normal breast epithelial cells and normal stem and early progenitor cells, selected by ALDH positivity. Wnt signaling was examined using a Topflash assay. Both curcumin and piperine inhibited mammosphere formation, serial passaging, and percent of ALDH+ cells by 50% at 5 μM and completely at 10 μM concentration in normal and malignant breast cells. There was no effect on cellular differentiation. Wnt signaling was inhibited by both curcumin and piperine by 50% at 5 μM and completely at 10 μM. Curcumin and piperine separately, and in combination, inhibit breast stem cell self-renewal but do not cause toxicity to differentiated cells. These compounds could be potential cancer preventive agents. Mammosphere formation assays may be a quantifiable biomarker to assess cancer preventive agent efficacy and Wnt signaling assessment can be a mechanistic biomarker for use in human clinical trials.

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Acknowledgements

This work was performed with NIH T32 grant, Innovative Concepts in Stem Cell Research Foundation Grant, and NIH KL2 grant support and support from the VA hospital. We are grateful to Sabinsa Co. for the donation of curcumin and piperine used in these experiments. The authors also wish to thank Irving L. Weissman (Stanford University School of Medicine, Stanford, California) for providing the LEF-1/TCF reporter constructs. We wish to thank Samadhi Liyanage and Dr. Shiv Kumar Dubey for their assistance with some experiments in this manuscript.

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Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Internal Medicine and Comprehensive Cancer Center, University of Michigan, 2150 Cancer Center, 1500 E. Medical Center Dr., Ann Arbor, MI, USA

    Madhuri Kakarala, Dean E. Brenner, Hasan Korkaya, Connie Cheng, Karim Tazi, Christophe Ginestier, Suling Liu, Gabriela Dontu & Max S. Wicha

  2. Department of Pharmacology, University of Michigan, 2150 Cancer Center, 1500 E. Medical Center Dr., Ann Arbor, MI, 48109, USA

    Dean E. Brenner

  3. VA Medical Center, Ann Arbor, MI, 48105, USA

    Madhuri Kakarala & Dean E. Brenner

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  1. Madhuri Kakarala
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Correspondence to Madhuri Kakarala.

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Kakarala, M., Brenner, D.E., Korkaya, H. et al. Targeting breast stem cells with the cancer preventive compounds curcumin and piperine. Breast Cancer Res Treat 122, 777–785 (2010). https://doi.org/10.1007/s10549-009-0612-x

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  • DOI: https://doi.org/10.1007/s10549-009-0612-x

Keywords

  • Breast stem cells
  • Cancer prevention
  • Curcumin
  • Piperine