Bromelain proteinases modulate the cd44 expression on human molt-4/8 leukemia and sk-mel-28 melanoma-cells in-vitro.

CD44 cell surface proteins are involved in leukocyte binding to endothelium and the metastatic spread of tumor cells. Using flow cytometric analysis (FCMA), we investigated the effects of the proteases bromelain, papain, trypsin, and chymotrypsin on the density of CD44 molecules present on human leukemia Molt 4/8 cells. Bromelain was found to be most active in reducing CD44 receptor density. In addition, the effects of the purified bromelain proteinases F4 and F9 were investigated. On Molt 4/8 cells crude bromelain and F9, with the highest proteolytical activity, were found to be most active in reducing CD44 receptor density with a half maximal value of 1.9 mu g/ml and 2.3 mu g/ml, respectively. On human SK-Mel 28 melanoma cells especially F9 showed a strong effect, with a half maximal value of 1.5 mu g/ml. The implications of the findings are discussed with view of the reported antimetastatic activity of orally administrated bromelain with respect to CD44.