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

Madhuri Kakarala1, Dean E Brenner, Hasan Korkaya

  • 1Division 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 48109, USA. mkakaral@umich.edu

Insights

Dietary compounds curcumin and piperine effectively inhibit breast cancer stem cell self-renewal and Wnt signaling without harming normal cells. These findings suggest potential cancer preventive applications.

Area of Science:

  • Oncology
  • Molecular Biology
  • Natural Products Chemistry

Background:

  • The cancer stem cell hypothesis posits that cancer originates from stem/progenitor cells with dysregulated self-renewal.
  • Identifying agents that modulate cancer stem cell self-renewal is crucial for cancer prevention and treatment.

Purpose of the Study:

  • To investigate the effects of dietary polyphenols curcumin and piperine on normal and malignant breast stem cell self-renewal.
  • To assess the impact of these compounds on aldehyde dehydrogenase (ALDH) expression and Wnt signaling pathways.

Main Methods:

  • Mammosphere formation assays were used to evaluate stem cell self-renewal capacity.
  • ALDH positivity was used to isolate normal stem and progenitor cells.
  • Wnt signaling activity was measured using a Topflash assay.

Main Results:

  • Curcumin and piperine significantly inhibited mammosphere formation and serial passaging in both normal and malignant breast cells.
  • Both compounds reduced the percentage of ALDH-positive cells by 50% at 5 microM and completely at 10 microM.
  • Wnt signaling was dose-dependently inhibited by curcumin and piperine, with complete inhibition at 10 microM.
  • No significant toxicity was observed in differentiated cells.

Conclusions:

  • Curcumin and piperine demonstrate potent inhibition of breast stem cell self-renewal and Wnt signaling.
  • These polyphenols exhibit potential as cancer preventive agents due to their targeted action on stem cells.
  • Mammosphere formation and Wnt signaling assays serve as valuable biomarkers for assessing the efficacy of cancer preventive agents.

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