Transcriptomic profiling of curcumin-treated human breast stem cells identifies a role for stearoyl-coa desaturase in breast cancer prevention.
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.
Department of Environmental Health Sciences, University of Michigan School of Public Health, 6630 SPH Tower, 1415 Washington Heights, Ann Arbor, MI, 48109, USA.|University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.|Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Justin A
http://orcid.org/0000-0002-5882-4569
JA
Colacino
University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
Sean P
SP
McDermott
University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.|Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
Maureen A
MA
Sartor
University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
Max S
MS
Wicha
Department of Environmental Health Sciences, University of Michigan School of Public Health, 6630 SPH Tower, 1415 Washington Heights, Ann Arbor, MI, 48109, USA. rozekl@umich.edu.|University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA. rozekl@umich.edu.
Laura S
LS
Rozek
D000470:Alkaloids / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D052117:Benzodioxoles / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics* / Q000517:prevention & control; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D003474:Curcumin / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D017423:Sequence Analysis, RNA / Q000379:methods*; D013230:Stearoyl-CoA Desaturase / Q000235:genetics*; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism
D000470:Alkaloids; D000970:Antineoplastic Agents; D052117:Benzodioxoles; D010880:Piperidines; D053284:Polyunsaturated Alkamides; C523776:SCD1 protein, human; D013230:Stearoyl-CoA Desaturase; D003474:Curcumin; C008922:piperine
Breast stem cell; Curcumin; Prevention; RNA-seq; Stearoyl-coa desaturase