RESUMEN

Glycan array analysis of Sclerotium rolfsii lectin (SRL) revealed its exquisite binding specificity to the oncofetal Thomsen-Friedenreich (Galß1-3GalNAcα-O-Ser/Thr, T or TF) antigen and its derivatives. This study shows that SRL strongly inhibits the growth of human colon cancer HT29 and DLD-1 cells by binding to cell surface glycans and induction of apoptosis through both the caspase-8 and -9 mediated signaling. SRL showed no or very weak binding to normal human colon tissues but strong binding to cancerous and metastatic tissues. Intratumor injection of SRL at subtoxic concentrations in NOD-SCID mice bearing HT29 xenografts resulted in total tumor regression in 9 days and no subsequent tumor recurrence. As the increased expression of TF-associated glycans is commonly seen in human cancers, SRL has the potential to be developed as a therapeutic agent for cancer.

Asunto(s)

Antígenos de Neoplasias/metabolismo , Antígenos de Carbohidratos Asociados a Tumores/metabolismo , Ascomicetos/química , Neoplasias del Colon/tratamiento farmacológico , Lectinas/uso terapéutico , Animales , Antígenos de Neoplasias/inmunología , Antígenos de Carbohidratos Asociados a Tumores/inmunología , Apoptosis/efectos de los fármacos , Caspasa 8/metabolismo , Caspasa 9/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Neoplasias del Colon/inmunología , Neoplasias del Colon/metabolismo , Humanos , Inyecciones , Lectinas/aislamiento & purificación , Lectinas/metabolismo , Ratones , Ratones Endogámicos NOD , Ratones SCID , Trasplante de Neoplasias , Neoplasias Experimentales , Polisacáridos/química , Polisacáridos/inmunología , Unión Proteica , Transducción de Señal/efectos de los fármacos