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Bromelain proteases as immunomodulators for therapy of mammary tumors

Maurer H.R.

Institute of Pharmacy, Free University of Berlin, Germany

International congress "Advances in Immunology and Allergology at the Treshold of the XXI Century" May 3-6, 2000, Eilat, Israel

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Bromelain is a mixture of acid and basic thiol proteases extracted from pineapple stems. As an oral drug it is used to treat, due to its antiplatelet and anticoagulating properties, thrombophlebitis, edemas and inflammatory diseases. Its claimed antimetastatic oral activity in mice has attracted our interest for further studies. An isolated basic fraction with highest protease activity showed a strong IL-2 like activity by stimulating human peripheral blood lymphocytes to kill SK-Mel 28 melanoma cells as well as to secrete TNF-a and IL-2 in vitro. In a preclinical study with 16 mammary tumor patients and 15 healthy donors oral administration of bromelain (3,000 FIP units daily for 10 days) doubled the capacity of isolated monocytes from the patients to kill K562 leukemic cells in vitro (MAK cell immunocytotoxicity). Patients leukocytes expressed lower MAK-, NK- and LAK-cell activities, compared with those from healthy donors. Bromelain responder patients showed less cytotoxicity before treatment than nonresponders, which was enhanced by bromelain about 7 fold, however. Thus oral bromelain reveals significant antitumor effects via monocytes (and probably dendritic cells). NK- and LAK-cells activities dropped during treatment, but normalized thereafter.

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