Anna Pawlik1, Marta Wała2, Aleksandra Hać1, Agnieszka Felczykowska3, Anna Herman-Antosiewicz4. 1. Department of Medical Biology and Genetics, University of Gdańsk, Wita Stwosza 59, Gdańsk 80-308, Poland. 2. Department of Medical Biology and Genetics, University of Gdańsk, Wita Stwosza 59, Gdańsk 80-308, Poland; Present address: Biomedical Engineering Centre, Institute of Optoelectronics, Military University of Technology, Kaliskiego 2, Warsaw 00-908, Poland. 3. Department of Bioenergetics and Physiology of Exercise, Medical University of Gdańsk, Dębinki 1, Gdańsk 80-211, Poland; Chair and Department of Physiology, Medical University of Gdańsk, Dębinki 1, Gdańsk 80-211, Poland. 4. Department of Medical Biology and Genetics, University of Gdańsk, Wita Stwosza 59, Gdańsk 80-308, Poland. Electronic address: anna.herman-antosiewicz@biol.ug.edu.pl.
Abstract
BACKGROUND: Isothiocyanates derived from the Brassicaceae plants possess chemopreventive and anticancer activities. One of them is sulforaphene (SF), which is abundant in Rhapanus sativus seeds. The underlying mechanism of its anticancer activity is still underexplored. PURPOSE: SF properties make it an interesting candidate for cancer prevention and therapy. Thus, it is crucial to characterize the mechanism of its activity. STUDY DESIGN: We investigated the mechanism of antiproliferative activity of SF in breast cancer cells differing in growth factor receptors status and lacking functional p53. METHODS: Viability of SKBR-3 and MDA-MB-231 breast cancer cells treated with SF was determined by SRB and clonogenic assays. Cell cycle, cell death and oxidative stress were analyzed by flow cytometry or microscopy. The levels of apoptosis and autophagy markers were assessed by immunoblotting. RESULTS: SF efficiently decreased the viability of breast cancer cells, while normal cells (MCF10A) were less sensitive to the analyzed isothiocyanate. SF induced G2/M cell cycle arrest, as well as disturbed cytoskeletal organization and reduced clonogenic potential of the cancer cells. SF induced apoptosis in a concentration-dependent manner which was associated with the oxidative stress, mitochondria dysfunction, increased Bax:Bcl2 ratio and ADRP levels. SF also potentiated autophagy which played a cytoprotective role. CONCLUSIONS: SF exhibits cytotoxic activity against breast cancer cells even at relatively low concentrations (5-10µM). This is associated with induction of the cell cycle arrest and apoptosis. SF might be considered as a potent anticancer agent.
BACKGROUND:Isothiocyanates derived from the Brassicaceae plants possess chemopreventive and anticancer activities. One of them is sulforaphene (SF), which is abundant in Rhapanus sativus seeds. The underlying mechanism of its anticancer activity is still underexplored. PURPOSE:SF properties make it an interesting candidate for cancer prevention and therapy. Thus, it is crucial to characterize the mechanism of its activity. STUDY DESIGN: We investigated the mechanism of antiproliferative activity of SF in breast cancer cells differing in growth factor receptors status and lacking functional p53. METHODS: Viability of SKBR-3 and MDA-MB-231 breast cancer cells treated with SF was determined by SRB and clonogenic assays. Cell cycle, cell death and oxidative stress were analyzed by flow cytometry or microscopy. The levels of apoptosis and autophagy markers were assessed by immunoblotting. RESULTS:SF efficiently decreased the viability of breast cancer cells, while normal cells (MCF10A) were less sensitive to the analyzed isothiocyanate. SF induced G2/M cell cycle arrest, as well as disturbed cytoskeletal organization and reduced clonogenic potential of the cancer cells. SF induced apoptosis in a concentration-dependent manner which was associated with the oxidative stress, mitochondria dysfunction, increased Bax:Bcl2 ratio and ADRP levels. SF also potentiated autophagy which played a cytoprotective role. CONCLUSIONS:SF exhibits cytotoxic activity against breast cancer cells even at relatively low concentrations (5-10µM). This is associated with induction of the cell cycle arrest and apoptosis. SF might be considered as a potent anticancer agent.
Authors: Besma Abbaoui; Christopher R Lucas; Ken M Riedl; Steven K Clinton; Amir Mortazavi Journal: Mol Nutr Food Res Date: 2018-08-29 Impact factor: 5.914
Authors: Paula García-Ibañez; Lucía Yepes-Molina; Antonio J Ruiz-Alcaraz; María Martínez-Esparza; Diego A Moreno; Micaela Carvajal; Pilar García-Peñarrubia Journal: Int J Mol Sci Date: 2020-12-10 Impact factor: 5.923