Bromelain Induces the Differentiation of Leukemic Cells in Vitro: An Explanation for its Cytostatic Effects?

Abstract

Bromelain is a mixture of proteases and other not yet identified enzymes isolated from pineapple stems and fruits and has been used for centuries against inflammatory diseases, burns, thrombophlebitis, edema, etc. More recently its antineoplastic activity has attracted interest, and various explanations for its mode of action have been proposed. Here we report that Bromelain is capable of inducing the differentiation of 3 leukemic cell lines in vitro. In M 1-T 22 cells, a myeloid mouse leukemia, Bromelain induces monocytic morphology, phagocytosis, and lysozyme activity; it inhibits cell growth concomit-antly. When Bromelain is pretreated either with heat or protease inhibitors, these effects are partially abolished. Similarily, in HL-60 cells, a human promyelocytic leukemia, Bromelain also induces monocytic morphology, non-specific esterase activity, and NBT reduction; it inhibits cell growth. Finally, K 562 cells, a human leukemia able to differentiate into the erythroid lineage, show hemoglobin-positive cells following exposure to Bromelain at relatively low concentrations.

These findings offer a possible explanation for the observed cytostatic potential of Bromelain in combination chemotherapy. Interestingly, such effects are seen in cancer patients even after oral administration of Bromelain, probably because Bromelain is glycosylated, which may protect it against the peptic and tryptic attack in the gastrointestinal tract. Further studies are needed to evaluate and extend these findings in vivo.