Prevention of Carcinogen-Induced Oral Cancer by Sulforaphane
Bauman JE, Zang Y, Sen M, Li C, Wang L, Egner PA, Fahey JW, Normolle DP, Grandis JR, Kensler TW, Johnson DE
Cancer prevention research (Philadelphia, Pa.) · 83 citations
How it was studied
- Design
- Controlled clinical trial (indexed by PubMed)
- Studied in
- People, plus animal or lab work
- Main outcome
- Clinical events such as disease or death
- Intake measured by
- Intake biomarkers
Who paid for it
- Funding
- Independent funding
- Government
- National Institutes of Health
- University or hospital
- Cancer Institute, University of Pittsburgh
- Government
- National Cancer Institute
- Government
- NIH
- Government
- NCI NIH HHS
- Nonprofit
- Lewis B. and Dorothy Cullman Foundation and also used UPCI
- Grants
- National Cancer Institute (P50 CA097190); National Cancer Institute (R35 CA197222); National Cancer Institute (R01 CA190610); National Cancer Institute (P30 CA 047904); National Institutes of Health (P30CA47904); National Institutes of Health (P50-CA097190); National Institutes of Health (R01CA190610 and R35CA197222)
Based on 6 listed funder(s).
Publication
- Published
- 2016-06-23 · Cancer Prev Res (Phila) · vol. 9 · issue 7 · pp. 547–557
- Publisher
- American Association for Cancer Research
- Cited
- 120 citations · more than 96% of similar papers · 4.9× the field average
- Impact
- Top 10% most cited in its field
- References
- 57 works
- Access
- Open access (repository copy)
- Research areas
- Genomics, phytochemicals, and oxidative stress · IL-33, ST2, and ILC Pathways · Bioactive Compounds and Antitumor Agents
- Keywords
- Sulforaphane, Carcinogen, Glucoraphanin, Cruciferous vegetables, Pharmacology, Cancer research, Cancer, Chemistry, Head and neck squamous-cell carcinoma, Medicine, Internal medicine, Biology, Head and neck cancer, Biochemistry, Glucosinolate, Brassica
- MeSH
- cell line, animals, mice, inbred c57bl, humans, mice, brassica, mouth neoplasms, isothiocyanates, sulfoxides, plant extracts, antineoplastic agents, phytogenic, carcinogens, pilot projects, cross-over studies, nf-e2-related factor 2
11 authors
From US
- Julie E. BaumanUniversity of Pittsburgh; UPMC Hillman Cancer Center
- Yan ZangUniversity of Pittsburgh
- Malabika SenUniversity of Pittsburgh
- Changyou LiUniversity of Pittsburgh
- Lin WangUniversity of Pittsburgh
- Patricia A. EgnerJohns Hopkins University
Abstract
Chronic exposure to carcinogens represents the major risk factor for head and neck squamous cell carcinoma (HNSCC). Beverages derived from broccoli sprout extracts (BSE) that are rich in glucoraphanin and its bioactive metabolite sulforaphane promote detoxication of airborne pollutants in humans. Herein, we investigated the potential chemopreventive activity of sulforaphane using in vitro models of normal and malignant mucosal epithelial cells and an in vivo model of murine oral cancer resulting from the carcinogen 4-nitroquinoline-1-oxide (4NQO). Sulforaphane treatment of Het-1A, a normal mucosal epithelial cell line, and 4 HNSCC cell lines led to dose- and time-dependent induction of NRF2 and the NRF2 target genes NQO1 and GCLC, known mediators of carcinogen detoxication. Sulforaphane also promoted NRF2-independent dephosphorylation/inactivation of pSTAT3, a key oncogenic factor in HNSCC. Compared with vehicle, sulforaphane significantly reduced the incidence and size of 4NQO-induced tongue tumors in mice. A pilot clinical trial in 10 healthy volunteers evaluated the bioavailability and pharmacodynamic activity of three different BSE regimens, based upon urinary sulforaphane metabolites and NQO1 transcripts in buccal scrapings, respectively. Ingestion of sulforaphane-rich BSE demonstrated the greatest, most consistent bioavailability. Mucosal bioactivity, defined as 2-fold or greater upregulation of NQO1 mRNA, was observed in 6 of 9 evaluable participants ingesting glucoraphanin-rich BSE; 3 of 6 ingesting sulforaphane-rich BSE; and 3 of 9 after topical-only exposure to sulforaphane-rich BSE. Together, our findings demonstrate preclinical chemopreventive activity of sulforaphane against carcinogen-induced oral cancer, and support further mechanistic and clinical investigation of sulforaphane as a chemopreventive agent against tobacco-related HNSCC. Cancer Prev Res; 9(7); 547-57. ©2016 AACR.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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