Nano-Encapsulated Taro Lectin Can Cross an in vitro Blood-Brain Barrier, Induce Apoptosis and Autophagy and Inhibit the Migration of Human U-87 MG Glioblastoma Cells

Raiane Vieira Cardoso,1 Patricia Ribeiro Pereira,1 Cyntia Silva Freitas,1 Anna Victoria De Freitas Silva,2 Victor Midlej,2 Carlos Adam Conte-Júnior,1 Vania Margaret Flosi Paschoalin1 1Departamento de Bioquímica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; 2Instituto Oswaldo Cruz, Rio de Janeiro, RJ, BrazilCorrespondence: Vania Margaret Flosi Paschoalin, Av. Athos da Silveira Ramos 149 – sala 545 - Cidade Universitária - 21941-909, Rio de Janeiro, RJ, Brazil, Tel +55213938-7362, Fax +55213938-7266, Email [email protected]: Tarin, purified from taro (Colocasia esculenta), promotes anticancer effect against glioblastoma cells, a heterogeneous and aggressive primary central nervous system tumor and one of the most challenging tumors for oncotherapy. If able to overcome the blood-brain barrier (BBB), tarin may comprise a natural defense against glioblastomas in a context of the development of novel drugs to control these malignant cell proliferations.Methods: The anticancer effects of nano-encapsulated tarin were tested against U-87 MG cells and the molecular mechanisms involved in cell proliferation control were assessed by flow cytometry and transmission electron microscopy (TEM) analyses. The scratch assay was performed to investigate cell migration capacity, while nano-encapsulated tarin transport across the BBB was tested on the hCMEC/D3 endothelial cell line.Results: Nano-encapsulated tarin induced autophagy in U-87 MG cells, characterized by the presence of autophagosomes as revealed by TEM and corroborating the flow cytometry analysis employing acridine orange. Additional ultrastructural changes, such as mitochondrial swelling, were also observed. The presence of apoptotic cells and caspase 3/7 activation indicate that nano-encapsulated tarin may also induce cell death through apoptosis. Glioblastoma cell proliferation was arrested in the G2/M cell cycle phase, and cell migration was delayed. Reduced cell proliferation and glioblastoma cell migration inhibition were significant, as tarin was efficiently transported across the BBB during in vitro assays.Conclusion: Nano-encapsulated tarin may be effectively employed to inhibit glioblastoma cell proliferation and migration, as this novel formulation can overcome the BBB and induces carcinoma cell apoptosis and autophagy. Furthermore, nano-encapsulated tarin may comprise a novel chemotherapeutic agent against different tumoral lines, as it is able to control glioblastoma tumor proliferation by the same molecular mechanisms previously reported for breast adenocarcinomas. Additional studies should be carried out to clarify if nano-encapsulated tarin has a general effect on distinct carcinoma lines. Keywords: Colocasia esculenta, GNA-related lectin, cell cycle arrest, caspase 3-7 activation, antitumoral lectin, transendothelial permeability