Int. J. Dev. Biol. 61: 43 - 52 (2017)

https://doi.org/10.1387/ijdb.160169rb

Vol 61, Issue 1-2

The natural compound sanguinarine perturbs the regenerative capabilities of planarians

Published: 3 March 2017

Linda Balestrini^1,#, Alessia Di Donfrancesco^1,#, Leonardo Rossi², Silvia Marracci¹, Maria E. Isolani³, Anna M. Bianucci⁴ and Renata Batistoni*^,1,5

¹Dipartimento di Biologia, Università di Pisa, ²Dipartimento di Medicina Clinica e Sperimentale, Università di Pisa, ³Dipartimento di Farmacia, Università di Pisa, Pisa, Italy, ⁴Istituto Nazionale per la Scienza e Tecnologia dei Materiali, Florence and ⁵Interdepartmental Research Center "Nutraceuticals and Food for Health" University of Pisa, Pisa, Italy

Abstract

The natural alkaloid sanguinarine has remarkable therapeutic properties and has been used for centuries as a folk remedy. This compound exhibits interesting anticancer properties and is currently receiving attention as a potential chemotherapeutic agent. Nevertheless, limited information exists regarding its safety for developing organisms. Planarians are an animal model known for their extraordinary stem cell-based regenerative capabilities and are increasingly used for toxicological and pharmacological studies. Here, we report that sanguinarine, at micromolar concentrations, perturbs the regeneration process in the planarian Dugesia japonica. We show that sanguinarine exposure causes defects during anterior regeneration and visual system recovery, as well as anomalous remodelling of pre-existing structures. Investigating the effects of sanguinarine on stem cells, we found that sanguinarine perturbs the transcriptional profile of early and late stem cell progeny markers. Our results indicate that sanguinarine exposure alters cell dynamics and induces apoptosis without affecting cell proliferation. Finally, sanguinarine exposure influences the expression level of H⁺, K⁺-ATPase α subunit, a gene of the P-type-ATPase pump family which plays a crucial role during anterior regeneration in planaria. On the whole, our data reveal that sanguinarine perturbs multiple mechanisms which regulate regeneration dynamics and contribute to a better understanding of the safety profile of this alkaloid in developing organisms.

Keywords

regeneration, planarian, gene expression, sanguinarine, developmental toxicology