Prevention of Carcinogen-Induced Oral Cancer by Sulforaphane.

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.

• Authors: Julie E Bauman, Yan Zang, Malabika Sen, Changyou Li, Lin Wang, Patricia A Egner, Jed W Fahey, Daniel P Normolle, Jennifer R Grandis, Thomas W Kensler, Daniel E Johnson
• Journal: Cancer prevention research (Philadelphia, Pa.) (Cancer Prev Res (Phila)) Vol. 9 Issue 7 Pg. 547-57 (Jul 2016) ISSN: 1940-6215 [Electronic] United States
• PMID: 27339168 (Publication Type: Clinical Trial, Journal Article)
• Copyright: ©2016 American Association for Cancer Research.

Chemical References

• Antineoplastic Agents, Phytogenic
• Carcinogens
• Isothiocyanates
• NF-E2-Related Factor 2
• NFE2L2 protein, human
• Plant Extracts
• Sulfoxides
• sulforaphane

Topics

• Animals
• Antineoplastic Agents, Phytogenic (pharmacology)
• Brassica
• Carcinogens (toxicity)
• Cell Line
• Cross-Over Studies
• Humans
• Isothiocyanates (pharmacology)
• Mice
• Mice, Inbred C57BL
• Mouth Neoplasms (prevention & control)
• NF-E2-Related Factor 2 (drug effects)
• Pilot Projects
• Plant Extracts (pharmacology)
• Sulfoxides