title: A novel acidic serine protease, ASPNJ inhibits proliferation, induces apoptosis and enhances chemo-susceptibility of acute promyelocytic leukemia cell.
abstract: 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.
authors.affiliation: Department of Biochemistry, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin, China; Laboratory of Metabolic Disease Research and Drug Development, China Medical University, Shenyang, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Ge
authors.forename: Qiqing
authors.initials: Q
authors.lastname: Bo
authors.forename: Xinyu
authors.initials: X
authors.lastname: Hong
authors.forename: Jiayue
authors.initials: J
authors.lastname: Cui
authors.forename: Xue
authors.initials: X
authors.lastname: Jiang
authors.forename: Min
authors.initials: M
authors.lastname: Hong
authors.forename: Jiankai
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003561:Cytarabine / Q000008:administration & dosage; D015536:Down-Regulation / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage; D004353:Drug Evaluation, Preclinical; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015801:Helminth Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000473:pathology; D009835:Oligochaeta / Q000201:enzymology; D057057:Serine Proteases / Q000008:administration & dosage / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D005343:Fibrinolytic Agents; D015801:Helminth Proteins; D003561:Cytarabine; D004317:Doxorubicin; D057057:Serine Proteases; C586428:acidic serine protease, Neanthes japonica
keywords: Acidic serine protease; Acute promyelocytic leukemia; Apoptosis; Chemo-susceptibility; Fibrinolytic enzyme; Human peripheral blood cells; NB4 cell