Poster Presentation 30th Lorne Cancer Conference 2018

Exploring the role of hERG channels in breast cancers, using novel urea compounds that modulate hERG function (#115)

Sara Al-Rawi 1 , Terri Meehan-Andrews 1 , Jasim Al-Rawi 1
  1. Latrobe University, Kennington, VIC, Australia

Increasing evidence indicates that ion channels are involved in the pathophysiology of cancer. The human ether-á-go-go-related gene (hERG) can be considered one of the most critical ion-channel encoding genes involved in the establishment, maintenance and progression of neoplastic growth. A benefit of focusing on modulation of ion channels in the biology of cancer cells is, that ion channel proteins can be easily accessed from extracellular environment which allows for lower drug doses which subsequently reduced side effects. Modulation of hERG channels, using a commercially available hERG channel modulator NS1643, inhibits proliferation and migration in breast cancer cells (MDA-MB-231 and MCF-7). Similar compounds have been developed, with varying levels of specificity to hERG channel function. Using in vitro breast cancer cell lines, we have explored the function of these compounds as potential anti-neoplastic therapeutics. The hERG channel activator NS1643 (1,3-bis-(2-hydroxy-5-trifluoromethyl-phenyl)-urea) caused inhibition of proliferation at concentration 10uM. Though it seems that the effect of the compound is more significant in MCF-7 cell line with gradual inhibition on cell number as the concentration increased [1]. Comparing the effect of these new compounds to NS1643, all compounds inhibited cell growth in MCF-7, and initiated cell cycle arrest at the G1 phase. But 2 compounds (JH28B and JH37B) also displayed this toxic effect in MDA cells, which was more significant than NS1643. Further exploration of these novel compounds is important as they appear to have higher efficacy and having similar benefits in different cancer types.



  1. 1.Perez-Neut, M., V.R. Rao, and S. Gentile, hERG1/Kv11.1 activation stimulates transcription of p21 (waf/cip) in breast cancer cells via a calcineurin-dependent mechanism. Oncotarget, 2016. 7(37): p. 58893-58902.