Evaluation of biodistribution of sulforaphane after administration of oral broccoli sprout extract in melanoma patients with multiple atypical nevi

Shawn Tahata, Shivendra V. Singh, Yan Lin, Eun Ryeong Hahm, Jan H. Beumer, Susan M. Christner, Uma N. Rao, Cindy Sander, Ahmad A. Tarhini, Hussein Tawbi, Laura K. Ferris, Melissa Wilson, Amy Rose, Catherine M. Dietz, Ellen Hughes, Jed W Fahey, Sancy A. Leachman, Pamela B. Cassidy, Lisa H. Butterfield, Hassane M. ZarourJohn M. Kirkwood

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Abstract

Broccoli sprout extract containing sulforaphane (BSESFN) has been shown to inhibit ultraviolet radiation-induced damage and tumor progression in skin. This study evaluated the toxicity and potential effects of oral BSE-SFN at three dosages. Seventeen patients who each had at least 2 atypical nevi and a prior history of melanoma were randomly allocated to 50, 100, or 200 mmol oral BSE-SFN daily for 28 days. Atypical nevi were photographed on days 1 and 28, and plasma and nevus samples were taken on days 1, 2, and 28. Endpoints assessed were safety, plasma and skin sulforaphane levels, gross and histologic changes, IHC for phospho-STAT3(Y705), Ki-67, Bcl-2,HMOX1, and TUNEL, plasma cytokine levels, and tissue proteomics. All 17 patients completed 28 days with no dose-limiting toxicities. Plasma sulforaphane levels pooled for days 1, 2, and 28 showed median postadministration increases of 120 ng/mL for 50 mmol, 206 ng/mL for 100 mmol, and 655 ng/mL for 200 mmol. Median skin sulforaphane levels on day 28 were 0.0, 3.1, and 34.1 ng/g for 50, 100, and 200 mmol, respectively. Plasma levels of proinflammatory cytokines decreased from day 1 to 28. The tumor suppressor decorin was increased from day 1 to 28. Oral BSE-SFN is well tolerated at daily doses up to 200 mmol and achieves dose-dependent levels in plasma and skin. A larger efficacy evaluation of 200 mmol daily for longer intervals is now reasonable to better characterize clinical and biological effects of BSE-SFN as chemoprevention for melanoma.

Original languageEnglish (US)
Pages (from-to)429-437
Number of pages9
JournalCancer Prevention Research
Volume11
Issue number7
DOIs
Publication statusPublished - Jul 1 2018

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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