CPP-Ts: a new intracellular calcium channel modulator and a promising tool for drug delivery in cancer cells

Sci Rep. 2018 Oct 3;8(1):14739. doi: 10.1038/s41598-018-33133-3.

Abstract

Scorpion sting envenoming impacts millions of people worldwide, with cardiac effects being one of the main causes of death on victims. Here we describe the first Ca2+ channel toxin present in Tityus serrulatus (Ts) venom, a cell penetrating peptide (CPP) named CPP-Ts. We show that CPP-Ts increases intracellular Ca2+ release through the activation of nuclear InsP3R of cardiomyocytes, thereby causing an increase in the contraction frequency of these cells. Besides proposing a novel subfamily of Ca2+ active toxins, we investigated its potential use as a drug delivery system targeting cancer cell nucleus using CPP-Ts's nuclear-targeting property. To this end, we prepared a synthetic CPP-Ts sub peptide14-39 lacking pharmacological activity which was directed to the nucleus of specific cancer cell lines. This research identifies a novel subfamily of Ca2+ active toxins and provides new insights into biotechnological applications of animal venoms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence / genetics
  • Animals
  • Calcium / chemistry*
  • Calcium Channels
  • Cell Line, Tumor
  • Cell-Penetrating Peptides / chemistry*
  • Cell-Penetrating Peptides / genetics
  • Cell-Penetrating Peptides / pharmacology
  • Cell-Penetrating Peptides / therapeutic use
  • Cytoplasm / drug effects
  • Drug Delivery Systems*
  • Humans
  • Neoplasms / drug therapy*
  • Scorpion Venoms / chemistry
  • Scorpions / chemistry

Substances

  • Calcium Channels
  • Cell-Penetrating Peptides
  • Scorpion Venoms
  • Calcium