Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.32 (bromelain)
 1,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The protease bromelain from pineapple was suggested for adjuvant therapy of malignant diseases. We studied immunological effects of an orally applied bromelain drug on 16 breast cancer patients in comparison with healthy donors. Bromelain was applied for 10 days with a daily dose of 3000 F.I.P. units and the immunocytotoxicity of blood monocytes and lymphocytes against the leukemic K562 and MDA-MB-231 mammary carcinoma target cells was determined in vitro. In addition, the expression of the cell surface markers CD44, CD16, CD11a and CD62L on lymphocytes and the secretion of IL-2 and IL-1beta from monocytes was measured. Patients leukocytes expressed lower bMAK-, MAK-, NK- and LAK-cell activities, compared with those from healthy donors. Orally applied bromelain increased the reduced bMAK- and MAK-cell activity of patients monocytes about 2-fold. When the patients were classified on the basis of bromelain effects on the monocytic cytotoxicity into bromelain responders and nonresponders, about 40% of the patients responded to bromelain with an increase of cytotoxicity from 7.8% to 54% (bMAK-cell activity) and from 16% to 47% (MAK-cell activity). Bromelain was less effective on the higher cytotoxicity of monocytes from healthy donors, but stimulated the secretion of IL-1beta from monocytes. In contrast, patient monocytes secreted no detectable IL-1beta, before, during and after bromelain treatment. Bromelain had no effects on the impaired patients NK- and LAK-cell activity, but reduced the LAK-cell activity of healthy donors. No IL-2 was found in the supernatants of untreated and treated lymphocytes from healthy donors. Bromelain reduced the expression of CD44, but weakly increased CD11a and CD62L expression on patient lymphocytes, whereas CD16 remained unchanged. In vitro bromelain application to lymphocytes had similar effects, with greater reduction rates of CD44 and CD16 expression. As to coagulation parameters in plasma of healthy donors, the activated partial thromboplastin time was increased from 38 to 46 sec, leaving prothrombin time and plasminogen unchanged. These data suggest, that orally applied bromelain stimulates the deficient monocytic cytotoxicity of mammary tumor patients, which may partially explain its proposed antitumor activity.
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PMID:Effects of oral bromelain administration on the impaired immunocytotoxicity of mononuclear cells from mammary tumor patients. 1052 79

Bromelain, a crude extract from pineapple stem containing various thiol proteases, has previously been suggested for adjuvant therapy of malignant diseases. We hence tested in vitro whether a highly purified bromelain proteinase (F9) would affect the antitumor activity by human peripheral blood lymphocytes (PBL) against MCF-7 breast cancer, KB squamous carcinoma and SK-MEL-28 melanoma cells. The antiproliferative effects by pretreated PBL were determined using the microculture tetrazolium (MTT) assay. All three cell lines were susceptible to F9-treated PBL and KB cells were selected to examine the kinetics, the dose dependency and the specificity of the F9 effects on PBL. Maximal antitumor effects were obtained when PBL were incubated with 25 mug/ml of F9 for 3 days at which the proteolytical activity of the added F9 was 1.6 U/mg. The F9-induced PBL antitumor activity was dependent on the applied proteolytical activity and abolished when F9 was inactivated by iodoacetamide. In contrast to F9, trypsin or pronase were not able to induce PBL-mediated growth inhibition of KB target cells. In response to F9, the concentration of interleukin-2 (IL-2) and tumor necrosis factor-a increased 10 and 19 fold in the PBL supernatant, respectively. F9 was found to synergize LAK cell activity in addition to suboptimal concentrations (0.625-2.5 U/ml) of rIL-2. In contrast to rIL-2-activated PBL, no cytolytic effect by F9-activated PBL was measured in the BCECF release assay, suggesting that F9 acts by a mechanism different from that of IL-2. F9 was also found to be growth inhibitory in the MTT assay, when it was directly added to the tumor cells: The concentration, at 50% growth inhibition by F9, was in the range of 25-38 mug/ml at which the proteolytical activity of the added F9 was 2.5 U/mg. On the basis of the present study we suggest that F9 alone, or in combination with rIL-2, may be used as a potential biological response modifier in specific immunotherapy of distinct cancer diseases.
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PMID:Bromelain proteinase-f9 augments human lymphocyte-mediated growth-inhibition of various tumor-cells in-vitro. 2155 75