The C-Type Lectin Hellericetin Negatively Regulates Cell Adhesion, Cell-Cell interactions, and Adipogensis.
Abstract: Normal cell homeostasis relies upon its capability to attach to the extracellular matrix (ECM) and attach and communicate with adjacent cells. Cells binding to the ECM, and to each other, require communication signaling mechanisms using cell surface receptors such as: integrins, cadherins, selectins, and insulin receptors. These receptors, and receptors like these, function in many biological processes such as cell migration, differentiation and apoptosis. These biological processes are often deregulated in cancer and other metabolic diseases. Understanding these cell interactions are imperative and warrant critical investigation; however there are limitations to the tools available to elucidate these precise and sequential cellular interactions. In this work, we have isolated a C-Type Lectin from the Crotalus oreganus helleri called Hellericetin (Hella-C). Hellericetin was purified using cationic exchange High-Performance Liquid Chromatography (HPLC) and was tested on skin cancer melanoma Sk-Mel-28 and Pre-Adipocytes 3T3-L1 cells. Hellericetin inhibited Sk-Mel-28 cell adhesion to fibronectin with an 50% inhibition concentration (IC50) of 7 µM. Additionally, after Hellericetin incubation, we found a change in morphology, but no cytotoxic or apoptotic activity was detected. Interestingly, we found that pErk was significantly increased at 30 min after the addition of Hellericetin. In an adipogenesis model using 3T3-L1 cells, Hellericetin induced significant inhibition of cellular triglyceride accumulation while this toxin did not induce pre-adipocytes differentiation to white adipocyte pathway. Our data shows promising biomedical applications for Hellericetin as a tool for understanding cell migration, differentiation, and apoptosis. Herein, Hellericetin may have links to understanding the pathologies of various diseases such as diabetes and cancer.
Jonathan Ortegon*, Shelby Szteiter, Robert Walls, Montamas Suntravat, Elda Sanchez, Jacob Galan
Judging Forms – Official judges only