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.