PMID- 19898931 OWN - NLM STAT- MEDLINE DCOM- 20101026 LR - 20220408 IS - 1573-7217 (Electronic) IS - 0167-6806 (Print) IS - 0167-6806 (Linking) VI - 122 IP - 3 DP - 2010 Aug TI - Targeting breast stem cells with the cancer preventive compounds curcumin and piperine. PG - 777-85 LID - 10.1007/s10549-009-0612-x [doi] AB - 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 microM and completely at 10 microM 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 microM and completely at 10 microM. 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. FAU - Kakarala, Madhuri AU - Kakarala M AD - 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 48109, USA. mkakaral@umich.edu FAU - Brenner, Dean E AU - Brenner DE FAU - Korkaya, Hasan AU - Korkaya H FAU - Cheng, Connie AU - Cheng C FAU - Tazi, Karim AU - Tazi K FAU - Ginestier, Christophe AU - Ginestier C FAU - Liu, Suling AU - Liu S FAU - Dontu, Gabriela AU - Dontu G FAU - Wicha, Max S AU - Wicha MS LA - eng GR - R01 CA129765/CA/NCI NIH HHS/United States GR - R01 CA129765-02/CA/NCI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20091107 PL - Netherlands TA - Breast Cancer Res Treat JT - Breast cancer research and treatment JID - 8111104 RN - 0 (Alkaloids) RN - 0 (Benzodioxoles) RN - 0 (Piperidines) RN - 0 (Polyunsaturated Alkamides) RN - 0 (Wnt Proteins) RN - EC 1.2.1.3 (Aldehyde Dehydrogenase) RN - IT942ZTH98 (Curcumin) RN - U71XL721QK (piperine) SB - IM MH - Aldehyde Dehydrogenase/metabolism MH - Alkaloids/administration & dosage MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Benzodioxoles/administration & dosage MH - Breast/drug effects/metabolism/*pathology MH - Breast Neoplasms/*drug therapy/metabolism/pathology MH - Cell Differentiation/drug effects MH - Cell Proliferation/drug effects MH - Cells, Cultured MH - Curcumin/administration & dosage MH - Female MH - Humans MH - Immunoenzyme Techniques MH - Neoplastic Stem Cells/*drug effects/metabolism/*pathology MH - Piperidines/administration & dosage MH - Polyunsaturated Alkamides/administration & dosage MH - Signal Transduction/drug effects MH - Wnt Proteins/metabolism PMC - PMC3039120 MID - NIHMS172393 EDAT- 2009/11/10 06:00 MHDA- 2010/10/27 06:00 PMCR- 2011/08/01 CRDT- 2009/11/10 06:00 PHST- 2009/10/16 00:00 [received] PHST- 2009/10/20 00:00 [accepted] PHST- 2009/11/10 06:00 [entrez] PHST- 2009/11/10 06:00 [pubmed] PHST- 2010/10/27 06:00 [medline] PHST- 2011/08/01 00:00 [pmc-release] AID - 10.1007/s10549-009-0612-x [doi] PST - ppublish SO - Breast Cancer Res Treat. 2010 Aug;122(3):777-85. doi: 10.1007/s10549-009-0612-x. Epub 2009 Nov 7.