Inhibition of MCF-7 breast cancer cell proliferation by a synthetic peptide derived from the C-terminal sequence of Orai channel

Abstract

Intracellular Ca²⁺ signals play many important cellular functions such as migration, proliferation and differentiation. Store-operated Ca²⁺ entry (SOCE) is a major route of Ca²⁺ entry in nonexcitable cells. The activation of SOCE requires engagement between stromal interaction molecule 1 (STIM1) molecules on the endoplasmic reticulum and Ca²⁺ release-activated Ca²⁺ (CRAC) channel Orais (Orai1-3) on the plasma membrane. Accumulating evidence indicates that SOCE plays critical roles in cancer cell proliferation, invasion and metastasis. Here, we used the synthetic intracellular peptides derived from the C-termini of Orai channels to treat the breast cancer cells. We have found that Orai3-CT peptide exhibits stronger binding to STIM1 than Orai1-CT, and Orai3-CT peptide acts in a dominant negative fashion, blocking the STIM1-Orai1 interaction and reducing the Ca²⁺ entry and proliferation of breast cancer cells.

Keywords: Breast cancer cell; Inhibition; Orai peptide; Proliferation.