Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells

Yanyan Li, Tao Zhang, Hasan Korkaya, Suling Liu, Hsiu Fang Lee, Bryan Newman, Yanke Yu, Shawn G. Clouthier, Steven J. Schwartz, Max S. Wicha, Duxin Sun

Research output: Contribution to journalArticle

330 Citations (Scopus)

Abstract

Purpose: The existence of cancer stem cells (CSCs) in breast cancer has profound implications for cancer prevention. In this study, we evaluated sulforaphane, a natural compound derived from broccoli/broccoli sprouts, for its efficacy to inhibit breast CSCs and its potential mechanism. Experimental Design: Aldefluor assay and mammosphere formation assay were used to evaluate the effect of sulforaphane on breast CSCs in vitro. A nonobese diabetic/severe combined immunodeficient xenograft model was used to determine whether sulforaphane could target breast CSCs in vivo, as assessed by Aldefluor assay, and tumor growth upon cell reimplantation in secondary mice. The potential mechanism was investigated using Western blotting analysis and β-catenin reporter assay. Results: Sulforaphane (1-5 μmol/L) decreased aldehyde dehydrogenase-positive cell population by 65% to 80% in human breast cancer cells (P < 0.01) and reduced the size and number of primary mammospheres by 8- to 125-fold and 45% to 75% (P < 0.01), respectively. Daily injection with 50 mg/kg sulforaphane for 2 weeks reduced aldehyde dehydrogenase-positive cells by >50% in nonobese diabetic/ severe combined immunodeficient xenograft tumors (P = 0.003). Sulforaphane eliminated breast CSCs in vivo, thereby abrogating tumor growth after the reimplantation of primary tumor cells into the secondary mice (P < 0.01). Western blotting analysis and β-catenin reporter assay showed that sulforaphane downregulated the Wnt/β-catenin self-renewal pathway. Conclusions: Sulforaphane inhibits breast CSCs and downregulates the Wnt/β-catenin self-renewal pathway. These findings support the use of sulforaphane for the chemoprevention of breast cancer stem cells and warrant further clinical evaluation.

Original languageEnglish (US)
Pages (from-to)2580-2590
Number of pages11
JournalClinical Cancer Research
Volume16
Issue number9
DOIs
StatePublished - May 1 2010

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Neoplastic Stem Cells
Brassica
Breast Neoplasms
Catenins
Replantation
Neoplasms
Heterografts
Down-Regulation
Western Blotting
Aldehyde Dehydrogenase
sulforafan
Chemoprevention
Growth
Research Design

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells. / Li, Yanyan; Zhang, Tao; Korkaya, Hasan; Liu, Suling; Lee, Hsiu Fang; Newman, Bryan; Yu, Yanke; Clouthier, Shawn G.; Schwartz, Steven J.; Wicha, Max S.; Sun, Duxin.

In: Clinical Cancer Research, Vol. 16, No. 9, 01.05.2010, p. 2580-2590.

Research output: Contribution to journalArticle

Li, Y, Zhang, T, Korkaya, H, Liu, S, Lee, HF, Newman, B, Yu, Y, Clouthier, SG, Schwartz, SJ, Wicha, MS & Sun, D 2010, 'Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells', Clinical Cancer Research, vol. 16, no. 9, pp. 2580-2590. https://doi.org/10.1158/1078-0432.CCR-09-2937
Li, Yanyan ; Zhang, Tao ; Korkaya, Hasan ; Liu, Suling ; Lee, Hsiu Fang ; Newman, Bryan ; Yu, Yanke ; Clouthier, Shawn G. ; Schwartz, Steven J. ; Wicha, Max S. ; Sun, Duxin. / Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells. In: Clinical Cancer Research. 2010 ; Vol. 16, No. 9. pp. 2580-2590.
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abstract = "Purpose: The existence of cancer stem cells (CSCs) in breast cancer has profound implications for cancer prevention. In this study, we evaluated sulforaphane, a natural compound derived from broccoli/broccoli sprouts, for its efficacy to inhibit breast CSCs and its potential mechanism. Experimental Design: Aldefluor assay and mammosphere formation assay were used to evaluate the effect of sulforaphane on breast CSCs in vitro. A nonobese diabetic/severe combined immunodeficient xenograft model was used to determine whether sulforaphane could target breast CSCs in vivo, as assessed by Aldefluor assay, and tumor growth upon cell reimplantation in secondary mice. The potential mechanism was investigated using Western blotting analysis and β-catenin reporter assay. Results: Sulforaphane (1-5 μmol/L) decreased aldehyde dehydrogenase-positive cell population by 65{\%} to 80{\%} in human breast cancer cells (P < 0.01) and reduced the size and number of primary mammospheres by 8- to 125-fold and 45{\%} to 75{\%} (P < 0.01), respectively. Daily injection with 50 mg/kg sulforaphane for 2 weeks reduced aldehyde dehydrogenase-positive cells by >50{\%} in nonobese diabetic/ severe combined immunodeficient xenograft tumors (P = 0.003). Sulforaphane eliminated breast CSCs in vivo, thereby abrogating tumor growth after the reimplantation of primary tumor cells into the secondary mice (P < 0.01). Western blotting analysis and β-catenin reporter assay showed that sulforaphane downregulated the Wnt/β-catenin self-renewal pathway. Conclusions: Sulforaphane inhibits breast CSCs and downregulates the Wnt/β-catenin self-renewal pathway. These findings support the use of sulforaphane for the chemoprevention of breast cancer stem cells and warrant further clinical evaluation.",
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AU - Li, Yanyan

AU - Zhang, Tao

AU - Korkaya, Hasan

AU - Liu, Suling

AU - Lee, Hsiu Fang

AU - Newman, Bryan

AU - Yu, Yanke

AU - Clouthier, Shawn G.

AU - Schwartz, Steven J.

AU - Wicha, Max S.

AU - Sun, Duxin

PY - 2010/5/1

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N2 - Purpose: The existence of cancer stem cells (CSCs) in breast cancer has profound implications for cancer prevention. In this study, we evaluated sulforaphane, a natural compound derived from broccoli/broccoli sprouts, for its efficacy to inhibit breast CSCs and its potential mechanism. Experimental Design: Aldefluor assay and mammosphere formation assay were used to evaluate the effect of sulforaphane on breast CSCs in vitro. A nonobese diabetic/severe combined immunodeficient xenograft model was used to determine whether sulforaphane could target breast CSCs in vivo, as assessed by Aldefluor assay, and tumor growth upon cell reimplantation in secondary mice. The potential mechanism was investigated using Western blotting analysis and β-catenin reporter assay. Results: Sulforaphane (1-5 μmol/L) decreased aldehyde dehydrogenase-positive cell population by 65% to 80% in human breast cancer cells (P < 0.01) and reduced the size and number of primary mammospheres by 8- to 125-fold and 45% to 75% (P < 0.01), respectively. Daily injection with 50 mg/kg sulforaphane for 2 weeks reduced aldehyde dehydrogenase-positive cells by >50% in nonobese diabetic/ severe combined immunodeficient xenograft tumors (P = 0.003). Sulforaphane eliminated breast CSCs in vivo, thereby abrogating tumor growth after the reimplantation of primary tumor cells into the secondary mice (P < 0.01). Western blotting analysis and β-catenin reporter assay showed that sulforaphane downregulated the Wnt/β-catenin self-renewal pathway. Conclusions: Sulforaphane inhibits breast CSCs and downregulates the Wnt/β-catenin self-renewal pathway. These findings support the use of sulforaphane for the chemoprevention of breast cancer stem cells and warrant further clinical evaluation.

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