TY - JOUR
T1 - Evaluation of biodistribution of sulforaphane after administration of oral broccoli sprout extract in melanoma patients with multiple atypical nevi
AU - Tahata, Shawn
AU - Singh, Shivendra V.
AU - Lin, Yan
AU - Hahm, Eun Ryeong
AU - Beumer, Jan H.
AU - Christner, Susan M.
AU - Rao, Uma N.
AU - Sander, Cindy
AU - Tarhini, Ahmad A.
AU - Tawbi, Hussein
AU - Ferris, Laura K.
AU - Wilson, Melissa
AU - Rose, Amy
AU - Dietz, Catherine M.
AU - Hughes, Ellen
AU - Fahey, Jed W.
AU - Leachman, Sancy A.
AU - Cassidy, Pamela B.
AU - Butterfield, Lisa H.
AU - Zarour, Hassane M.
AU - Kirkwood, John M.
N1 - Funding Information:
This work was supported by NIH R21CA161951-Pilot Clinical-Pathological and Molecular Analysis of Atypical Nevi in Response to BSE-L-Sulforaphane. This project used the UPMC Hillman Cancer Center Cancer Pharmacokinetics and Pharmacodynamics Facility (CPPF) and Immunologic Monitoring and Cellular Products Laboratory (IMCPL) supported in part by award P30CA047904. We would like to acknowledge Lisa Huntley and Victoria Alisasis for their assistance in the preparation of this manuscript. We would also like to thank Mike Hoffelder, Dr. Paul Haley, and Kevin Mitchell from Computer Vision Group, Veytel, LLC for their expertise in performing the nevus image analysis, and Dr. Robert Parise for his assistance with modifications to the liquid chromatographic-mass spectrometric assay.
Publisher Copyright:
© 2018 American Association for Cancer Research.
PY - 2018/7
Y1 - 2018/7
N2 - 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.
AB - 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.
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U2 - 10.1158/1940-6207.CAPR-17-0268
DO - 10.1158/1940-6207.CAPR-17-0268
M3 - Article
C2 - 29691233
AN - SCOPUS:85049587168
SN - 1940-6207
VL - 11
SP - 429
EP - 437
JO - Cancer Prevention Research
JF - Cancer Prevention Research
IS - 7
ER -