Study of the antitumoral mechanism of tarin, a lectin from taro (Colocasia esculenta L. Schott), in its free or nano-encapsulated forms, in pre-clinical trials in carcinoma models

Abstract

Tarin is a purified lectin from yam (Colocasia esculenta L. Schott), belonging to the family of lectins related to GNA (Galanthus nivalis agglutinin), which has outstanding immunomodulatory and antitumor properties. When nano-encapsulated in pegylated liposomes, tarin has its stability and bioavailability increased, promoting controlled and sustained release, which enhances its biological effects and reduces cytotoxicity on normal cells. The present study evaluated the molecular mechanisms involved in the antitumor activity of nano-encapsulated tarin in two human tumoral cell lines treated for 24 and 48 h, the breast adenocarcinoma (MDA-MB-231) and glioblastoma (U-87 MG), two in vitro models widely used to study therapies against aggressive tumors. The analyses were conducted by flow cytometry, transmission electron microscopy (TEM) and cell migration assay (scratch assay) and proteomics. In addition, the transport of nano-encapsulated tarin across the blood-brain barrier (BBB) model was evaluated using hCMEC/D3 endothelial cells, demonstrating that the formulation is able to cross BBB efficiently, which reinforces its potential for the treatment of tumors from the central nervous system. Exposure to nano-encapsulated tarin also resulted in significant inhibition of cell proliferation and migration, without causing cytotoxic effects on healthy human fibroblasts. Nano-encapsulated tarin induces cell tumoral death by apoptosis and autophagy-dependent mechanisms. Treated-tumoral cells showed increased autophagosome formation, activation of caspases 3/7 and cell cycle arrest in the G0/G1 phases forMDA-MB-231 cells, and G2/M for U-87 MG A global proteomic analysis using mass spectrometry was performed to identify changes in protein expression and to clarify the molecular mechanisms involved in the cellular response to the antitumor formulation. The treatment modulated key proteins such as PARK7, OPA1, CHEK1, LAMA4, and HLA-A, indicating effects on oxidative stress regulation, mitochondrial dynamics, cell-cycle control, extracellular matrix remodeling, and antigen presentation. These alterations suggest that the action of nano-encapsulated tarin goes beyond direct cytotoxicity, promoting a functional reprogramming that destabilizes tumor homeostasis and favors the coordinated activation of cell death pathways. It seems that the cell death involves several processes that occur in an interdependent way, where the initial stress induced by exposition to tarin triggers autophagic responses, followed by the activation of apoptotic mechanisms and, consequently, by the inhibition of cell proliferation and migration. Together, these findings show that nano-encapsulated tarin exerts a multifactorial antitumor effect, acting on different pathways to control cell survival, and reinforce its potential as a promising candidate for the development of innovative and selective antitumor therapies, applicable to different types of human carcinoma, including breast cancer and glioblastoma.