Abstract B38: Exploring targeting potassium channels in cancer: A novel strategy for therapeutic intervention

We present data showing for the first time that pharmacologic stimulation of specific K+ channels with small molecules strongly reduced tumor growth and metastatic spread in different animal model of cancer biology including Drosophila and mice without discernible side effects.For example, use of two chemically distinct Kv11.1 potassium channel activators showed growth arrest in an in vivo Drosophila tumor model and strongly inhibited tumor growth in SCID mice bearing the aggressive TNBC cell line MDA-MB-231.In addition, the metastatic spread of this cancer cell line in NOD-scid-IL2Rnull was significantly reduced in terms of organs affected and metastatic burden.Interestingly, analysis of the biochemical signaling linking activation of specific K+ channels to tumor growth inhibition revealed that pharmacological stimulation of K+ channel activated a cellular senescent program that is characterized by increased expression of the tumor suppressors (e.g. p21, p16, HMGA2), formation of heterochromatin and permanent growth arrest of cancer cells independently of their molecular subtypes (including p53 negative cancer cells, breast, skin or ovarian cancer cells).Investigating on the possible mechanism linking Kv11.1 stimulation to inhibition of metastasis revealed that Kv11.1 agonists strongly inhibit cancer cell motility by suppressing nuclear function of bβ-catenin in transcribing for Epithelial to Mesenchymal Transition (EMT) markers including vimentin, CD44, N-cadherin. Co...
Source: Molecular Cancer Therapeutics - Category: Cancer & Oncology Authors: Tags: Chemical Biology: Poster Presentations - Proffered Abstracts Source Type: research