A novel acidic serine protease, ASPNJ inhibits proliferation, induces apoptosis and enhances chemo-susceptibility of acute promyelocytic leukemia cell

Acidic serine protease (ASPNJ) purified from Neanthes japonica, is a fibrinolytic enzyme. Earthworm fibrinolytic enzyme has been recently reported with anti-tumor activity on human hepatoma cells. To investigate if ASPNJ play therapeutic effects on emergent blood cancer, acute promyelocytic leukemia (APL), we tested the effects of ASPNJ on APL cell line NB4. Our results showed that ASPNJ inhibited the growth of NB4 cells in a dose and time dependent manner. Cell apoptosis was induced by ASPNJ with obvious morphological changes. The sensitivity of cells to cytarabine and doxorubicin were greatly increased respectively by combination with ASPNJ. In contrast to inhibitory effects on NB4 cells, ASPNJ showed much less effect on normal human neutrophils survival. There were no effects of hemolysis and agglutination observed on normal human erythrocytes following ASPNJ treatment. Conclusively, our data suggest that ASPNJ may become a new candidate for leukemia therapeutic approaches.