Sulforaphane Suppresses the Growth of Triple-negative Breast Cancer Stem-like Cells <i>In vitro</i> and <i>In vivo</i>
Castro NP, Rangel MC, Merchant AS, MacKinnon G, Cuttitta F, Salomon DS, Kim YS
Cancer prevention research (Philadelphia, Pa.) · 70 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- In vitro/mechanistic study (classified by our AI screen)
- Studied in
- People, plus animal or lab work
- Main outcome
- Mechanisms only
Who paid for it
- Funding
- Independent funding
- Government
- National Institutes of Health
- Government
- National Cancer Institute
- Government
- HHS | NIH | National Cancer InstituteHHS | NIH | National Cancer Institute (NCI)
- Government
- Intramural NIH HHS
- Grants
- National Institutes of Health (Z99 CA999999)
Based on 4 listed funder(s).
Publication
- Published
- 2019-01-24 · Cancer Prev Res (Phila) · vol. 12 · issue 3 · pp. 147–158
- Publisher
- American Association for Cancer Research
- Cited
- 102 citations · more than 95% of similar papers · 4.0× the field average
- Impact
- Top 10% most cited in its field
- References
- 37 works
- Access
- Open access (repository copy)
- Research areas
- Genomics, phytochemicals, and oxidative stress · Reproductive System and Pregnancy · Estrogen and related hormone effects
- Keywords
- Sulforaphane, In vivo, In vitro, Triple-negative breast cancer, Breast cancer, Cancer research, Stem cell, Cancer, Cancer stem cell, Oncology, Medicine, Biology, Internal medicine, Cell biology, Genetics
- MeSH
- tumor cells, cultured, animals, mice, inbred balb c, humans, mice, mice, nude, cell transformation, neoplastic, isothiocyanates, sulfoxides, anticarcinogenic agents, xenograft model antitumor assays, apoptosis, cell proliferation, female, neoplastic stem cells, transcriptome, triple negative breast neoplasms, in vitro techniques
7 authors
From US
- Nadia Pereira de Castro
- María Cristina Rangel
- Anand S. MerchantCenter for Cancer Research
- Gabriel MacKinnon
- Frank F. Cuttitta
- David S. Salomon
Abstract
Triple-negative breast cancer (TNBC) represents the poorest prognosis among all of breast cancer subtypes with no currently available effective therapy. In this study, we hypothesized that sulforaphane, a dietary component abundant in broccoli and its sprouts, can inhibit malignant cell proliferation and tumor sphere formation of cancer stem-like cells (CSC) in TNBC. CSC population was isolated using FACS analysis with the combined stem cell surface markers, CD44+/CD24-/CD49f+ The effect of sulforaphane on a stem-related embryonic oncogene CRIPTO-1/TDGF1 (CR1) was evaluated via ELISA. In vivo, BalbC/nude mice were supplemented with sulforaphane before and after TNBC cell inoculation (daily intraperitoneal injection of 50 mg sulforaphane/kg for 5 and 3 weeks, respectively), and the effects of sulforaphane during mammary tumor initiation and growth were accessed with NanoString gene analysis. We found that sulforaphane can inhibit cell proliferation and mammosphere formation of CSCs in TNBC. Further analysis of gene expression in these TNBC tumor cells revealed that sulforaphane significantly decreases the expression of cancer-specific CR1, CRIPTO-3/TDGF1P3 (CR3, a homologue of CR1), and various stem cell markers including Nanog, aldehyde dehydrogenase 1A1 (ALDH1A1), Wnt3, and Notch4. Our results suggest that sulforaphane may control the malignant proliferation of CSCs in TNBC via Cripto-mediated pathway by either suppressing its expression and/or by inhibiting Cripto/Alk4 protein complex formation. Thus, the use of sulforaphane for chemoprevention of TNBC is plausible and warrants further clinical evaluation.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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