Abstract
Abstract Background: Epidemiological studies showed higher intake of cruciferous vegetables or their active compounds, isothiocyanates (ITCs), with lower risk of lung cancer. ITCs inhibited tobacco-carcinogen induced lung adenocarcinoma in animal models, along with reduced cellular proliferative marker Ki-67 and increased apoptotic markers Caspase-3 and TUNEL. However, human data lack. The aim of our study was to assess if oral intake of sulforaphane (SFN) for 12 months would stop/reverse the progression of bronchial histopathology, reduce Ki-67 index and/or increase Caspase-3 and TUNEL indices. Methods: A randomized clinical trial (NCT03232138) was conducted in former smokers with ≥ 30 pack-years and quitting smoking for 1-10 years in USA. Forty-three subjects were randomly assigned to the SFN (n = 21) or placebo group (n = 22) in 2018-2022. Each participant was instructed to take 4 Avmacol® or identical placebo capsules BID for 12 months. Each Avmacol® capsule contained 15 mg of glucoraphanin, which yielded a daily internal dose of 120 μmol SFN. Biopsies were collected from 6 predetermined bronchial sites at baseline and the end of treatment, respectively. The primary outcomes were the average changes of histopathology scores, Ki-67, Caspase-3 and TUNEL indices in post- vs. pre-treatment biopsies. Results: Thirty-seven participants completed the study. In the SFN group (n = 17) at baseline, 13 were men, all white, mean age 64.1 (SD 5.3) years, body mass index (BMI) 30.6 (6.1) kg/m2, years of smoking 39.5 (8.2), cigarettes per day (CPD) 23.8 (10.7), and years of quitting smoking 4.3 (2.9). The corresponding figures in the placebo group (n=20) were 9 men, 19 white, age 68.0 (3.2), BMI 28.6 (4.2), years of smoking 42.2 (4.5), CPD 25.5 (8.4), and years of quitting smoking 6.8 (3.2). The baseline medians of total Ki-67 positive nuclei were 22.3 nuclei/mm2 in the SFN group and 22.9/mm2 in the placebo group (p = 0.96). After treatment, the number of positive Ki-67 nuclei decreased by 5.3/mm2 (-24%) in the SFN group and increased by 18.0/mm2 (+79%) in the placebo group (p = 0.014) with adjustment for baseline Ki-67 and other covariates. The post- and pre-treatment difference was even greater in high-density (3+) positive Ki-67, with -46% decrease in the SFN group vs. +99% increase in the placebo group (p = 0.004). There was a dose-response effect of higher compliance with SFN intake on reducing Ki-67 index (ptrend = 0.01). SFN treatment had no impact on Caspase-3, TUNEL, or bronchial histopathology. No severe adverse event was observed in the SFN group. Conclusion: Daily intake of 120 μmol SFN for 12 months significantly reduced Ki-67 index in bronchial tissue. The findings support the potential chemopreventive effect of SFN against lung cancer development in high-risk former smokers (Grant # R01CA213123). Citation Format: Jian-Min Yuan, Thomas W. Kensler, Sanja Dacic, Douglas J. Harman, Renwei Wang, Paula Balogh, Lindsey Seigh, Yen T-H Pham, Jennifer Adams-Haduch, Shivendra Singh, James G. Herman, Avrum Spira, David O. Wilson. Randomized placebo-controlled phase II clinical trial on oral supplementation of sulforaphane for 12 months that reduced bronchial Ki-67 index in former smokers at high risk for lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 749.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.