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BIBTEX RIS

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

2018; Nature Portfolio; Volume: 8; Issue: 1 Linguagem: Inglês

10.1038/s41598-018-33133-3

2045-2322

Bárbara Bruna Ribeiro Oliveira-Mendes, Carolina Campolina Rebello Horta, Anderson Oliveira do Carmo, Gabriela Lago Biscoto, Douglas Ferreira Sales-Medina, Hortênsia Gomes Leal, Pedro F. P. Brandão‐Dias, Sued Eustáquio Mendes Miranda, Carla Aguiar, Valbert Nascimento Cardoso, André Luís Branco de Barros, Carlos Chávez-Olórtegui, M. Fátima Leite, Evanguedes Kalapothakis,

Venomous Animal Envenomation and Studies

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.