We used a sudden-expansion flow chamber to examine U-937 cell adhesion to unactivated and tumor necrosis factor (TNF)-α-activated human umbilical vein endothelial cells (HUVEC) in recirculating flow. For both unactivated and TNF-α-activated HUVEC, U-937 cells exhibited transient arrests within ∼150 μm of flow reattachment. Few arrests occurred directly at the reattachment site. U-937 cell rolling was not observed. At all other locations within the recirculation zone, U-937 cells did not exhibit transient arrests or rolling. TNF-α activation increased the frequency of U-937 cell arrests near reattachment but did not change the median arrest duration. Numerically simulated cell trajectories failed to predict attachment near the reattachment point. Deviations between experiment and theory may result from the nonspherical shape and deformability of U-937 cells. These results demonstrate that U-937 cell transient arrests occur preferentially in the vicinity of the reattachment point in recirculating flow. Possible mechanisms for adhesion include low shear stress, curved streamlines, fluid velocity components normal to the endothelium, and formation of larger contact areas.

Cytotoxic membrane disruption via lytic peptides is a well-recognized mechanism of immune surveillance for antifungal and antibacterial host protection. Naturally occurring lytic peptides were shown to exhibit antitumor activity as well. Peptidyl membrane-interactive molecules (MIMs) are synthetic lytic peptides specifically designed to maximize antitumor activity. We tested nine novel Peptidyl MIMs for activity against four androgen-insensitive prostate-cancer cell lines using a standard microculture tetrazolium (MTT) assay. Five Peptidyl MIMs known to form alpha-helical secondary structures were active against prostate carcinoma and were chosen for further study. Three peptides configured in beta-pleated sheets were noticeably less effective. Concentrations lethal to 50% of the prostate-cancer cell lines treated (D50 values) with the five chosen Peptidyl MIMs ranged from 0.6 to 1.8 microM. For comparison, two alpha-helically structured peptides, D2A21 and DP1E, were tested on several other cancer types: breast (n = 2), colon (n = 2). bladder, cervical and lung carcinomas (n = 1 each). Resulting LD50 values obtained in breast carcinoma cells were significantly higher (P < 0.05) than those observed in prostate cancer cells. LD50 values recorded for D2A21 and DP1E in cervical, colon, bladder, and lung cancer lines were similar to those obtained in prostate cancer cells. As compared with cisplatin, a standard chemotherapeutic drug, the LD50 values recorded for D2A21 were significantly lower (P < 0.04) in prostate-cancer cell lines, suggesting the therapeutic efficacy of Peptidyl MIMs. These data demonstrate for the first time the cytotoxic potential of Peptidyl MIMs against prostate cancer cells and suggest a dependence on a specific secondary alpha-helical structure of the peptide.