Jian‐Min Yuan,Thomas W. Kensler,Sanja Đačić,Douglas J. Hartman,Renwei Wang,Paula Balogh,Pamela Sufka,Melissa A. Turner,Kimberly Fuhrer,Lindsey Seigh,Yen Thi-Hai Pham,Jennifer Adams‐Haduch,Giuseppe Valacchi,Shivendra V. Singh,James G. Herman,David O. Wilson
出处
期刊:Cancer Prevention Research [American Association for Cancer Research] 日期:2025-03-05
Experimental studies have shown dietary isothiocyanates reduced cellular proliferative marker Ki-67 and increased apoptotic markers Caspase-3 and TUNEL in animals, but human data are lacking. The present study was to assess whether sulforaphane would stop/reverse the progression of bronchial histopathology, reduce Ki-67 index and/or increase Caspase-3 and TUNEL indices in humans. A randomized clinical trial (NCT03232138) was conducted in former smokers. Forty-three subjects were randomly assigned to the placebo or the treatment with a potential daily dose of 95 µmol sulforaphane for 12 months. The endpoints were the changes of histopathology scores, and Ki-67, Caspase-3 and TUNEL indices in post- vs. pre-treatment bronchial biopsies. Thirty-seven participants (17 in the sulforaphane and 20 in the placebo group) completed the study. Supplementation of sulforaphane did not show significant impact on bronchial histopathology, but significantly reduced Ki-67 index with a 20% decrease in the sulforaphane group and a 65% increase in the placebo (p = 0.014). The difference was even greater in high-density (3+) positive Ki-67, with a 44% decrease in the sulforaphane group compared with a 71% increase in the placebo (p = 0.004). Higher bioavailability of sulforaphane was correlated with greater reduction of Ki-67 index (P for trend = 0.019). Sulforaphane treatment had no impact on Caspase-3 or TUNEL index in bronchial biopsies. No severe adverse event was observed in the study participants. The findings of oral sulforaphane that significantly reduced Ki-67 index in bronchial tissue support further development as a potential chemopreventive agent against lung cancer development.