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 language | English (US) |
|---|---|
| Pages (from-to) | 2580-2590 |
| Number of pages | 11 |
| Journal | Clinical Cancer Research |
| Volume | 16 |
| Issue number | 9 |
| DOIs | |
| State | Published - May 1 2010 |
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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 journal › Article
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TY - JOUR
T1 - Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells
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
Y1 - 2010/5/1
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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77951730125&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77951730125&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-09-2937
DO - 10.1158/1078-0432.CCR-09-2937
M3 - Article
C2 - 20388854
AN - SCOPUS:77951730125
VL - 16
SP - 2580
EP - 2590
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 9
ER -