Int. J. Dev. Biol. 61: 43 - 52 (2017)
doi: 10.1387/ijdb.160169rb
© UPV/EHU Press

The natural compound sanguinarine perturbs the regenerative capabilities of planarians

Linda Balestrini1,#, Alessia Di Donfrancesco1,#, 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

*Corresponding author e-mail: renata.batistoni@unipi.it