Abstract
Objective Leukemia is a cancer of the blood cells. Leukemic THP-1 and U937 cells were used in this study as monocytic effectors cells for proliferation responses and macrophage-like cells induction in leukemia. Pardaxin is an antimicrobial peptide isolated from the marine fish species. Methods After treatment for 5 days, pardaxin significantly suppressed cell viability and arrested cell cycle at G0/G1 phase in leukemic cells which were evaluated. Results Pardaxin also induced cell differentiation and maturation of THP-1 and U937 cells into macrophage-like cells with phagocytotic ability. Moreover, pardaxin elevated the expression of MyD88 but not toll-like receptor (TLR)-2 in both leukemic cells. TLR-2 blocking peptide was used to confirm that pardaxin attenuated phagocytotic ability and superoxide anion production in leukemic cells via activating MyD88 protein. Conclusions These findings suggested that pardaxin has a therapeutic potential for leukemia.
Highlights
Antimicrobial peptides (AMPs) have been known to belong to a huge family of peptide molecules that typically contain less than 100 amino acids and they exist in various types of cells in vertebrates and invertebrates
In order to confirm the mechanism of pardaxin on toll-like receptor (TLR)-2/MyD88 pathway and leukemic cell maturation, TLR2 block peptide was used to suppress TLR-2 activation and MyD88 expression, and the results demonstrated that pardaxin treatment for 5 days significantly increased MyD88 level in leukemic THP-1 and U937 cells, but this effect was abolished by treatment with TLR-2 blocking peptide (Figure 5)
Similar results were found in superoxide anion production and phagocytotic ability in leukemic THP-1 cells (Figure 6) and U937 cells (Figure 7), and the elevations of superoxide anion production and phagocytotic ability by treatment with pardaxin for 5 days were attenuated by TLR2 blocking peptide treatment in leukemic THP-1 and U937 cells
Summary
Leukemia is a cancer of the blood cells. Leukemic THP-1 and U937 cells were used in this study as monocytic effectors cells for proliferation responses and macrophage-like cells induction in leukemia. Pardaxin is an antimicrobial peptide isolated from the marine fish species. After treatment for 5 days, pardaxin significantly suppressed cell viability and arrested cell cycle at G0/G1 phase in leukemic cells which were evaluated. Pardaxin induced cell differentiation and maturation of THP-1 and U937 cells into macrophage-like cells with phagocytotic ability. Pardaxin elevated the expression of MyD88 but not toll-like receptor (TLR)-2 in both leukemic cells. TLR-2 blocking peptide was used to confirm that pardaxin attenuated phagocytotic ability and superoxide anion production in leukemic cells via activating MyD88 protein. These findings suggested that pardaxin has a therapeutic potential for leukemia
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