Sanguine Byun1,2,3, Seung Ho Shin4,5, Jiman Park2,6, Semi Lim2, Eunjung Lee2,7, Chaeyoon Lee8, Dongeun Sung8, Lee Farrand2, Seoung Rak Lee9, Ki Hyun Kim9, Zigang Dong4, Sam W Lee3, Ki Won Lee1,2. 1. Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea. 2. WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seou, Republic of Korea. 3. Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA. 4. Department of Cellular and Molecular Biology, The Hormel Institute, University of Minnesota, Austin, MN, USA. 5. Program in Biomedical Informatics and Computational Biology, University of Minnesota, Minneapolis, MN, USA. 6. Research Center, Ottogi Corp, Gyeonggi-Do, Republic of Korea. 7. Traditional Alcoholic Beverage Research Team, Korea Food Research Institute, Seongnam, Republic of Korea. 8. Department of Food Science & Engineering, Ewha Womans University, Seoul, Korea. 9. School of Pharmacy, Sungkyunkwan University, Suwon, Korea.
Abstract
SCOPE: Cruciferous vegetables harbor a number of isothiocyanates that have been recognized for their cancer-related properties. Out of these, sulforaphene (a naturally occurring derivative of sulforaphane) has received little attention in studies of colon cancer and its mechanism of action remains to be elucidated. METHODS AND RESULTS: We observed that sulforaphene inhibited growth of human colon cancer cell lines HCT116, HT-29, KM12, SNU-1040, and DLD-1, while exhibiting negligible toxicity toward nonmalignant cells. Sulforaphene induced G2/M phase cell cycle arrest and apoptosis of colon cancer cells analyzed by flow cytometry, concomitant with phosphorylation of CDK1 and CDC25B at inhibitory sites, and upregulation of the p38 and JNK pathways. It was further determined that sulforaphene is a potent inhibitor of microtubule polymerization while generating reactive oxygen species via the depletion of glutathione. These observations further extended into inhibitory effects against colon tumor growth in a mouse xenograft model. CONCLUSION: These findings demonstrate that sulforaphene may contribute to the anti-tumor effects of cruciferous vegetables that contain sulforaphene and other isothiocyanates.
SCOPE: Cruciferous vegetables harbor a number of isothiocyanates that have been recognized for their cancer-related properties. Out of these, sulforaphene (a naturally occurring derivative of sulforaphane) has received little attention in studies of colon cancer and its mechanism of action remains to be elucidated. METHODS AND RESULTS: We observed that sulforaphene inhibited growth of humancolon cancer cell lines HCT116, HT-29, KM12, SNU-1040, and DLD-1, while exhibiting negligible toxicity toward nonmalignant cells. Sulforaphene induced G2/M phase cell cycle arrest and apoptosis of colon cancer cells analyzed by flow cytometry, concomitant with phosphorylation of CDK1 and CDC25B at inhibitory sites, and upregulation of the p38 and JNK pathways. It was further determined that sulforaphene is a potent inhibitor of microtubule polymerization while generating reactive oxygen species via the depletion of glutathione. These observations further extended into inhibitory effects against colon tumor growth in a mouse xenograft model. CONCLUSION: These findings demonstrate that sulforaphene may contribute to the anti-tumor effects of cruciferous vegetables that contain sulforaphene and other isothiocyanates.
Authors: Eva Juengel; Sebastian Maxeiner; Jochen Rutz; Saira Justin; Frederik Roos; Wael Khoder; Igor Tsaur; Karen Nelson; Wolf O Bechstein; Axel Haferkamp; Roman A Blaheta Journal: Oncotarget Date: 2016-12-20
Authors: Barbara Tomasello; Maria Domenica Di Mauro; Giuseppe Antonio Malfa; Rosaria Acquaviva; Fulvia Sinatra; Giorgia Spampinato; Samuele Laudani; Giusy Villaggio; Anna Bielak-Zmijewska; Wioleta Grabowska; Ignazio Alberto Barbagallo; Maria Teresa Liuzzo; Elisabetta Sbisà; Maria Grazia Forte; Claudia Di Giacomo; Massimo Bonucci; Marcella Renis Journal: Int J Mol Sci Date: 2020-07-27 Impact factor: 5.923