Immunomodulatory and anti-tumor activities of native and heat denatured Abrus agglutinin

Abstract

Abrus agglutinin (AAG), a hetero tetrameric gal β (1–3) NAc gal specific lectin, is isolated from seeds of Abrus precatorius. In our previous studies we found that the protein could act as an immunomodulator and immunoadjuvant in native (NA) and heat denatured (HDA) conditions. An anticancer effect of the lectin is reported, but its mode of action is not clearly known. In the present study, the anti-tumor activity of AAG (NA, HDA) has been evaluated in a murine Dalton's lymphoma (DL) ascites tumorogenic model. We found that treatment with both NA and HDA were able to decrease the tumor cell number in vivo and significantly increased median survival time. In vitro studies showed that AAG (NA, HDA) treatment of Dalton's lymphoma ascites cells (DLAC) resulted in growth inhibition at the concentration of 1 μg/ml and above. Whereas, AAG (NA, HDA) at much lower concentrations (∼1 ng/ml) can stimulate peritoneal macrophage and spleen derived NK cells in vitro demonstrating cytotoxicity against DLAC. Cell cycle analysis showed an increased number of cells in Sub-G 0/G 1 phase for in vitro and in vivo treatments. In summary, AAG (NA, HDA) at non-toxic concentration was able to elicit anti-tumor effects in DL bearing mice by stimulating the innate immune system and Th1 type immunomodulation.