Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 1/2016

01-07-2016 | Preclinical study

Transcriptomic profiling of curcumin-treated human breast stem cells identifies a role for stearoyl-coa desaturase in breast cancer prevention

Authors: Justin A. Colacino, Sean P. McDermott, Maureen A. Sartor, Max S. Wicha, Laura S. Rozek

Published in: Breast Cancer Research and Treatment | Issue 1/2016

Login to get access

Abstract

Curcumin is a potential agent for both the prevention and treatment of cancers. Curcumin treatment alone, or in combination with piperine, limits breast stem cell self-renewal, while remaining non-toxic to normal differentiated cells. We paired fluorescence-activated cell sorting with RNA sequencing to characterize the genome-wide changes induced specifically in normal breast stem cells following treatment with these compounds. We generated genome-wide maps of the transcriptional changes that occur in epithelial-like (ALDH+) and mesenchymal-like (ALDH−/CD44+/CD24−) normal breast stem/progenitor cells following treatment with curcumin and piperine. We show that curcumin targets both stem cell populations by down-regulating expression of breast stem cell genes including ALDH1A3, CD49f, PROM1, and TP63. We also identified novel genes and pathways targeted by curcumin, including downregulation of SCD. Transient siRNA knockdown of SCD in MCF10A cells significantly inhibited mammosphere formation and the mean proportion of CD44+/CD24− cells, suggesting that SCD is a regulator of breast stemness and a target of curcumin in breast stem cells. These findings extend previous reports of curcumin targeting stem cells, here in two phenotypically distinct stem/progenitor populations isolated from normal human breast tissue. We identified novel mechanisms by which curcumin and piperine target breast stem cell self-renewal, such as by targeting lipid metabolism, providing a mechanistic link between curcumin treatment and stem cell self-renewal. These results elucidate the mechanisms by which curcumin may act as a cancer-preventive compound and provide novel targets for cancer prevention and treatment.
Appendix
Available only for authorised users
Literature
1.
2.
Brandberg Y et al (2008) Psychological reactions, quality of life, and body image after bilateral prophylactic mastectomy in women at high risk for breast cancer: a prospective 1-year follow-up study. J Clin Oncol 26(24):3943–3949CrossRefPubMed
3.
Fisher B et al (1998) Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 90(18):1371–1388CrossRefPubMed
4.
Vogel VG et al (2010) Update of the national surgical adjuvant breast and bowel project study of tamoxifen and raloxifene (STAR) P-2 Trial: preventing breast cancer. Cancer Prev Res (Phila) 3(6):696–706CrossRef
5.
Howell A (2008) The endocrine prevention of breast cancer. Best Pract Res Clin Endocrinol Metab 22(4):615–623CrossRefPubMed
6.
Noorafshan A, Ashkani-Esfahani S (2013) A review of therapeutic effects of curcumin. Curr Pharm Des 19(11):2032–2046PubMed
7.
Shoba G et al (1998) Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med 64(4):353–356CrossRefPubMed
8.
9.
Kakarala M et al (2010) Targeting breast stem cells with the cancer preventive compounds curcumin and piperine. Breast Cancer Res Treat 122(3):777–785CrossRefPubMed
10.
Molyneux G et al (2010) BRCA1 basal-like breast cancers originate from luminal epithelial progenitors and not from basal stem cells. Cell Stem Cell 7(3):403–417CrossRefPubMed
11.
12.
Van Keymeulen A et al (2011) Distinct stem cells contribute to mammary gland development and maintenance. Nature 479(7372):189–193CrossRefPubMed
13.
Liu S et al (2013) Breast cancer stem cells transition between epithelial and mesenchymal states reflective of their normal counterparts. Stem Cell Reports 2(1):78–91CrossRefPubMedPubMedCentral
14.
15.
Robinson MD, McCarthy DJ, Smyth GK (2010) edgeR: a bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26(1):139–140CrossRefPubMed
16.
Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B (Methodological), p 289–300
17.
Lim E et al (2009) Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers. Nat Med 15(8):907–913CrossRefPubMed
18.
Svedberg J et al (1990) Free-fatty acid inhibition of insulin binding, degradation, and action in isolated rat hepatocytes. Diabetes 39(5):570–574CrossRefPubMed
19.
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25(4):402–408CrossRefPubMed
20.
R Core Team R: A language and environment for statistical computing. 2013: R Foundation for Statistical Computing, Vienna, Austria
21.
Eirew P et al (2012) Aldehyde dehydrogenase activity is a biomarker of primitive normal human mammary luminal cells. Stem Cells 30(2):344–348CrossRefPubMed
22.
Keller PJ et al (2012) Defining the cellular precursors to human breast cancer. Proc Natl Acad Sci USA 109(8):2772–2777CrossRefPubMed
23.
Isfoss BL et al (2013) Women with familial risk for breast cancer have an increased frequency of aldehyde dehydrogenase expressing cells in breast ductules. BMC Clin Pathol 13(1):28CrossRefPubMedPubMedCentral
24.
25.
Zhong Y et al (2013) Expression of ALDH1 in breast invasive ductal carcinoma: an independent predictor of early tumor relapse. Cancer Cell Int 13(1):60CrossRefPubMedPubMedCentral
26.
Sheridan C et al (2006) CD44+/CD24− breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis. Breast Cancer Res 8(5):R59CrossRefPubMedPubMedCentral
27.
28.
Yang C et al (2009) Curcumin upregulates transcription factor Nrf2, HO-1 expression and protects rat brains against focal ischemia. Brain Res 1282:133–141CrossRefPubMed
29.
McNally SJ et al (2007) Curcumin induces heme oxygenase 1 through generation of reactive oxygen species, p38 activation and phosphatase inhibition. Int J Mol Med 19(1):165–172PubMed
30.
Motterlini R et al (2000) Curcumin, an antioxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress. Free Radic Biol Med 28(8):1303–1312CrossRefPubMed
31.
Shen SQ et al (2007) Protective effect of curcumin against liver warm ischemia/reperfusion injury in rat model is associated with regulation of heat shock protein and antioxidant enzymes. World J Gastroenterol 13(13):1953–1961CrossRefPubMedPubMedCentral
32.
Dunsmore KE, Chen PG, Wong HR (2001) Curcumin, a medicinal herbal compound capable of inducing the heat shock response. Crit Care Med 29(11):2199–2204CrossRefPubMed
33.
34.
Lee CH et al (2012) Inhibition of heat shock protein (Hsp) 27 potentiates the suppressive effect of Hsp90 inhibitors in targeting breast cancer stem-like cells. Biochimie 94(6):1382–1389CrossRefPubMed
35.
36.
Charpentier MS et al (2014) Curcumin targets breast cancer stem-like cells with microtentacles that persist in mammospheres and promote reattachment. Cancer Res 74(4):1250–1260CrossRefPubMed
37.
Whipple RA et al (2008) Vimentin filaments support extension of tubulin-based microtentacles in detached breast tumor cells. Cancer Res 68(14):5678–5688CrossRefPubMedPubMedCentral
38.
Bhardwaj RK et al (2002) Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4. J Pharmacol Exp Ther 302(2):645–650CrossRefPubMed
39.
Duangjai A et al (2013) Black pepper and piperine reduce cholesterol uptake and enhance translocation of cholesterol transporter proteins. J Nat Med 67(2):303–310CrossRefPubMed
40.
Hong J et al (2004) Modulation of arachidonic acid metabolism by curcumin and related β-diketone derivatives: effects on cytosolic phospholipase A2, cyclooxygenases and 5-lipoxygenase. Carcinogenesis 25(9):1671–1679CrossRefPubMed
41.
Lev-Ari S et al (2006) Down-regulation of prostaglandin E2 by curcumin is correlated with inhibition of cell growth and induction of apoptosis in human colon carcinoma cell lines. J Soc Integr Oncol 4(1):21–26PubMed
42.
Kudo C et al (2011) Novel curcumin analogs, GO-Y030 and GO-Y078, are multi-targeted agents with enhanced abilities for multiple myeloma. Anticancer Res 31(11):3719–3726PubMed
43.
Shin HS et al (2014) Anti-atherosclerosis and hyperlipidemia effects of herbal mixture, Artemisia iwayomogi Kitamura and Curcuma longa Linne, in apolipoprotein E-deficient mice. J Ethnopharmacol 153(1):142–150CrossRefPubMed
44.
Igal RA (2010) Stearoyl-CoA desaturase-1: a novel key player in the mechanisms of cell proliferation, programmed cell death and transformation to cancer. Carcinogenesis 31(9):1509–1515CrossRefPubMed
45.
46.
Mauvoisin D et al (2013) Decreasing stearoyl-CoA desaturase-1 expression inhibits beta-catenin signaling in breast cancer cells. Cancer Sci 104(1):36–42CrossRefPubMed
47.
Rios-Esteves J, Marilyn Resh D (2013) Stearoyl CoA desaturase is required to produce active, lipid-modified Wnt proteins. Cell Rep 4(6):1072–1081CrossRefPubMed
48.
Metadata
Title
Transcriptomic profiling of curcumin-treated human breast stem cells identifies a role for stearoyl-coa desaturase in breast cancer prevention
Authors
Justin A. Colacino
Sean P. McDermott
Maureen A. Sartor
Max S. Wicha
Laura S. Rozek
Publication date
01-07-2016
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 1/2016
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-016-3854-4

Other articles of this Issue 1/2016

Breast Cancer Research and Treatment 1/2016 Go to the issue

Epidemiology

Measured adolescent body mass index and adult breast cancer in a cohort of 951,480 women

Preclinical study

Proliferation assessment in breast carcinomas using digital image analysis based on virtual Ki67/cytokeratin double staining

Brief Report

Genomic landscape of small cell carcinoma of the breast contrasted to small cell carcinoma of the lung

Clinical trial

Palbociclib as a first-line treatment in oestrogen receptor-positive, HER2-negative, advanced breast cancer not cost-effective with current pricing: a health economic analysis of the Swiss Group for Clinical Cancer Research (SAKK)

Clinical trial

Phase I biomarker modulation study of atorvastatin in women at increased risk for breast cancer

Clinical trial

Computerized patient identification for the EMBRACA clinical trial using real-time data from the PRAEGNANT network for metastatic breast cancer patients
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits