In vitro activity: Bestatin inhibits proliferation of all the human leukemic cell lines except KG1. Bestatin induces DNA fragmentation quantitatively and DNA ladder and enhances caspase-3 activity in U937 cells. Bestatin dose-dependently induces DNA fragmentation in human leukemic cell lines. Bestatin dose-dependently inhibits the invasion of SN12M cells into reconstituted basement membrane (Matrigel). Bestatin inhibits the degradation of type IV collagen by tumor cells, but not by tumor-conditioned medium (TCM), in a concentration-dependent manner. Bestatin inhibits hydrolysing activities towards substrates of aminopeptidases in SN12M cells. Bestatin inhibits the tube-like formation of human umbilical vein endothelial cells (HUVECs) in vitro. Bestatin exerts a direct stimulating effect on lymphocytes (and monocytes) via its fixation on cell surface leucine-aminopeptidase, and an indirect effect on monocytes (and lymphocytes) via aminopeptidase B inhibition of tuftsin catabolism.

Cell Assay: To determine the interaction and the possible role of APN in MDR, RT–PCR was performed to detect the mRNA levels of APN and MDR1 in K562 and K562/ADR cells. After incubation with various concentration of bestatin for 24 h, the expression of APN mRNA was almost unchanged in K562 and K562/ADR cells. However, K562/ADR cells exhibited a significant lower level of APN mRNA than K562 cells. On the other hand, high dose of bestatin (100 μM) induced MDR1 upregulation by 49.4% and 18.0% in K562 and K562/ADR cells, respectively. The result confirmed that bestatin was a substrate of P-gp in mRNA level.

Leukemia. 1999 May;13(5):729-34; Clin Exp Metastasis. 1992 Jan;10(1):49-59; Cancer Lett. 2004 Dec 8;216(1):35-42.