title: Effects of selenium compounds on proliferation and epigenetic marks of breast cancer cells.
abstract: Breast cancer is a global public health problem and the most frequent cause of cancer death among women. Mammary carcinogenesis is driven not only by genetic alterations but also by epigenetic disturbances. Because epigenetic marks are potentially reversible they represent promising molecular targets for breast cancer prevention interventions. Selenium is a promising anti-breast cancer trace element that has shown the modulation of DNA methylation and histone post-translational modifications in other malignancies. This study aimed to evaluate the effects of selenium compounds [methylseleninic acid (MSA) and selenite] on cell proliferation and death, expression of the tumor suppressor gene RASSF1A and epigenetic marks in MCF-7 human breast adenocarcinoma cells. Treatment with MSA or selenite markedly inhibited (P<0.05) in a dose-dependent manner the proliferation of MCF-7 cells. MSA induced (P<0.05) G2/M cell arrest while selenite presented the opposite effect. Regarding cell death induction, MSA acted mainly by inducing apoptosis (P<0.05), while selenite only induced necrosis (P<0.05). Furthermore selenite, but not MSA, markedly induced (P<0.05) cytotoxicity and increased (P<0.05) RASSF1A expression. Both selenium compounds inhibited (P<0.05) DNMT1 expression. MSA decreased (P<0.05) H3K9me3 and increased (P<0.05) H4K16ac, while selenite decreased (P<0.05) this latter histone mark. To the best of our knowledge this is the first report showing that selenite and MSA modulate epigenetic marks specifically in breast cancer cells. Our data reinforce the anti-breast cancer potential of selenium that is dependent on its chemical form. Furthermore the data show that epigenetic mechanisms represent relevant molecular targets involved in selenium inhibitory effects in breast cancer cells.
authors.affiliation: Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Juliana Xavier
authors.initials: JX
authors.lastname: de Miranda
authors.affiliation: Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Fábia de Oliveira
authors.initials: Fde O
authors.lastname: Andrade
authors.affiliation: Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Aline de
authors.initials: Ad
authors.lastname: Conti
authors.affiliation: Department of Pathology, School of Veterinary Medicine and Animal Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Maria Lúcia Zaidan
authors.initials: ML
authors.lastname: Dagli
authors.affiliation: Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Fernando Salvador
authors.initials: FS
authors.lastname: Moreno
authors.affiliation: Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil. Electronic address: tong@usp.br.
authors.forename: Thomas Prates
authors.initials: TP
authors.lastname: Ong
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects / Q000235:genetics*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D016566:Organoselenium Compounds / Q000494:pharmacology; D020887:Selenious Acid / Q000494:pharmacology; D018036:Selenium Compounds / Q000494:pharmacology*; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D016566:Organoselenium Compounds; C411762:RASSF1 protein, human; D018036:Selenium Compounds; D025521:Tumor Suppressor Proteins; C008493:methylselenic acid; D020887:Selenious Acid
keywords: Apoptosis; Epigenetic marks; MCF-7 breast cancer cells; Selenium