Potassium channel activation inhibits proliferation of breast cancer cells by activating a senescence program Journal Article

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Authors: Lansu, K.; Gentile, S
Article Title: Potassium channel activation inhibits proliferation of breast cancer cells by activating a senescence program
Abstract: Traditionally the hERG1 potassium channel has been known to have a fundamental role in membrane excitability of several mammalian cells including cardiac myocytes. hERG1 has recently been found to be expressed in non-excitable cancer cells of different histogenesis, but the role of this channel in cancer biology is unknown. Results form recent studies on the effect hERG1 inhibition in some breast cancer cells are controversial as it can lead to apoptosis or protect against cell death. Nevertheless, these data suggest that the hERG1 channel could have an important role in cancer biology. Here we report the effects of hyperstimulation of hERG1 channel in human mammary gland adenocarcinoma-derived cells. Application of the hERG1 activator, the diphenylurea derivative NS1643, inhibits cell proliferation irreversibly. This event is accompanied by a preferential arrest of the cell cycle in G0/G1 phase without the occurrence of apoptotic events. Consequently, cells responded to NS1643 by developing a senescence-like phenotype associated with increased protein levels of the tumor suppressors p21 and p16(INK4a) and by a positive beta-galactosidase assay. These data suggest that prolonged stimulation of the hERG1 potassium channel may activate a senescence program and offers a compelling opportunity to develop a potential antiproliferative cancer therapy.
Journal Title: Cell death disease
Volume: 4
ISSN: 2041-4889
Publisher: Unknown  
Journal Place: England
Date Published: 2013
Start Page: e652
Language: eng
DOI/URL:

10.1038/cddis.2013.174

10.1038/cddis.2013.174
Notes: JID: 101524092; epublish