Evaluation of Biodistribution of Sulforaphane after Administration of Oral Broccoli Sprout Extract in Melanoma Patients with Multiple Atypical Nevi

Cancer Prev Res (Phila). 2018 Jul;11(7):429-438. doi: 10.1158/1940-6207.CAPR-17-0268. Epub 2018 Apr 24.

Abstract

Broccoli sprout extract containing sulforaphane (BSE-SFN) 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 μmol 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 μmol, 206 ng/mL for 100 μmol, and 655 ng/mL for 200 μmol. Median skin sulforaphane levels on day 28 were 0.0, 3.1, and 34.1 ng/g for 50, 100, and 200 μmol, 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 μmol and achieves dose-dependent levels in plasma and skin. A larger efficacy evaluation of 200 μmol daily for longer intervals is now reasonable to better characterize clinical and biological effects of BSE-SFN as chemoprevention for melanoma. Cancer Prev Res; 11(7); 429-38. ©2018 AACR.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism
  • Biopsy
  • Brassica / chemistry*
  • Capsules
  • Feasibility Studies
  • Female
  • Humans
  • Isothiocyanates / administration & dosage*
  • Isothiocyanates / adverse effects
  • Isothiocyanates / pharmacokinetics
  • Male
  • Melanoma / pathology
  • Melanoma / prevention & control*
  • Middle Aged
  • Nevus / drug therapy*
  • Nevus / pathology
  • Plant Extracts / administration & dosage*
  • Plant Extracts / adverse effects
  • Plant Extracts / pharmacokinetics
  • Pregnancy
  • Skin / drug effects
  • Skin / pathology
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology
  • Tissue Distribution
  • Treatment Outcome
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Capsules
  • Isothiocyanates
  • Plant Extracts
  • sulforaphane