Bromelain Proteinases Modulate the Cd44 Expression on Human Molt-4/8 Leukemia and Sk-Mel-28 Melanoma-Cells in-Vitro

Harrach, T.; Gebauer, Frank; Eckert, Kristin A.; Kunze, Rachel; Maurer, H. R.

doi:10.3892/ijo.5.3.485

Cited by 20 publications

(18 citation statements)

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“…The effects of bromelain on the cell surface molecules reported here are in agreement with those in several smaller and previous studies (9,12,17,18). However, in one study reporting that oral bromelain slightly reduced the expression of CD44 on human PBL in vivo, CD62L and CD16 were described as unchanged (14).…”

Section: Figsupporting

confidence: 82%

Bromelain Treatment Alters Leukocyte Expression of Cell Surface Molecules Involved in Cellular Adhesion and Activation

Hale

Greer²,

Sempowski

2002

Clinical Immunology

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Section: Figsupporting

confidence: 82%

Bromelain Treatment Alters Leukocyte Expression of Cell Surface Molecules Involved in Cellular Adhesion and Activation

Hale

Greer²,

Sempowski

2002

Clinical Immunology

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“…The adhesion molecule CD44 has attracted particular interest since it was recognized as a marker for circulating cells, especially metastasizing tumor cells [59]. Harrach et al [57] showed that bromelain diminished CD44 expression on Molt 4/8 leukemia and SK-Mel 28 melanoma cells, the effect being most pronounced with bromelain fraction F9, with its high proteolytical activity. Yet the proteinase activity of the bromelain fractions tested did not correlate with the manner in which CD44 expression could be modulated.…”

Section: Bromelain Modulates the Function Of Cell Adhesion Moleculesmentioning

confidence: 99%

Bromelain: biochemistry, pharmacology and medical use

Maurer¹

2001

CMLS, Cell. Mol. Life Sci.

566

429

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Bromelain is a crude extract from the pineapple that contains, among other components, various closely related proteinases, demonstrating, in vitro and in vivo, antiedematous, antiinflammatory, antithrombotic and fibrinolytic activities. The active factors involved are biochemically characterized only in part. Due to its efficacy after oral administration, its safety and lack of undesired side effects, bromelain has earned growing acceptance and compliance among patients as a phytotherapeutical drug. A wide range of therapeutic benefits has been claimed for bromelain, such as reversible inhibition of platelet aggregation, angina pectoris, bronchitis, sinusitis, surgical traumas, thrombophlebitis, pyelonephritis and enhanced absorption of drugs, particularly of antibiotics. Biochemical experiments indicate that these pharmacological properties depend on the proteolytic activity only partly, suggesting the presence of nonprotein factors in bromelain. Recent results from preclinical and pharmacological studies recommend bromelain as an orally given drug for complementary tumor therapy: bromelain acts as an immunomodulator by raising the impaired immunocytotoxicity of monocytes against tumor cells from patients and by inducing the production of distinct cytokines such as tumor necrosis factor-a, interleukin (Il)-1beta, Il-6, and Il-8. In a recent clinical study with mammary tumor patients, these findings could be partially confirmed. Especially promising are reports on animal experiments claiming an antimetastatic efficacy and inhibition of metastasis-associated platelet aggregation as well as inhibition of growth and invasiveness of tumor cells. Apparently, the antiinvasive activity does not depend on the proteolytic activity. This is also true for bromelain effects on the modulation of immune functions, its potential to eliminate burn debris and to accelerate wound healing. Whether bromelain will gain wide acceptance as a drug that inhibits platelet aggregation, is antimetastatic and facilitates skin debridement, among other indications, will be determined by further clinical trials. The claim that bromelain cannot be effective after oral administration is definitely refuted at this time.

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“…Trypsin may cleave the extracellular matrix components either directly [21] or indirectly via activation of metalloproteases [17]. In addition, interaction of proteases with certain adhesion molecules (CD4, CD44 and B7-1) was demonstrated, while many others remain untouched [13,20].…”

Section: Discussionmentioning

confidence: 99%

The effect of oral protease administration in the rat remnant kidney model

et al. 1999

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It has been demonstrated that intraperitoneal administration of proteolytic enzymes ameliorates the progression of renal diseases in various animal models. In the present study, we employed the rat remnant kidney model to study the effectiveness of oral administration of proteases. Twenty male Wistar rats underwent sham operation (CTRL), while 25 were subjected to 5/6 nephrectomy (5/6 NX). Rats were randomised into placebo (PL) (2 ml tap water/day by gavage), or Phlogenzym (E; fixed mixture of trypsin 2.42 mg, bromelain 4.54 mg, and rutozid 5.04 mg added as antioxidant, in 2 ml tap water daily by gavage) treated group. Duration of the study was 45 days. Rats were pair-fed. Enzyme treatment exerted salutary effects on various functional and morphological parameters. Proteinuria was higher in both 5/6 NX group rats throughout the study. Administration of proteases ameliorated its rise effectively (data at sacrifice: CTRL-PL 6.27 +/- 1.25, CTRL-E 9.27 +/- 0.99, 5/6 NX-PL 74.04 +/- 21.33, 5/6 NX-E 39.09 +/- 7.93 mg/24 h; P < 0.01). Increased urinary excretion of the fibrogenic cytokine transforming growth factor (TGF-beta 1) was improved, too (CTRL-PL 0.349 +/- 0.051, CTRL-E 0.693 +/- 0.230, 5/6 NX-PL 3.044 +/- 0.540, 5/6 NX-E 1.390 +/- 0.238 ng/mumol creatinine; P < 0.05). At sacrifice, tubulointerstitial fibrosis was less pronounced in E-treated rats. Correspondingly, the volume fraction of tubulointerstitial tissue in the renal cortex was improved in 5/6 NX-E rats (CTRL-PL 9.9 +/- 0.2, CTRL-E 10.0 +/- 0.2, 5/6 NX-PL 17.9 +/- 1.8, 5/6 NX-E 13.8 +/- 0.9%; P < 0.05). The protein/DNA ratio in isolated glomeruli and tubules, as an estimate of glomerular matrix accumulation and hypertrophy of tubules, was enhanced in 5/6 NX groups and a tendency towards lower values was observed after E treatment. Renal function as evaluated by serum creatinine and urea levels was not influenced by the enzyme therapy. No between-group differences in blood pressure were observed. In summary, oral administration of proteolytic enzymes improved proteinuria and urinary TGF-beta 1 excretion, as well as the severity of tubulointerstitial fibrosis without signs of toxicity.

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Bromelain Proteinases Modulate the Cd44 Expression on Human Molt-4/8 Leukemia and Sk-Mel-28 Melanoma-Cells in-Vitro

Cited by 20 publications

References 0 publications

Bromelain Treatment Alters Leukocyte Expression of Cell Surface Molecules Involved in Cellular Adhesion and Activation

Bromelain Treatment Alters Leukocyte Expression of Cell Surface Molecules Involved in Cellular Adhesion and Activation

Bromelain: biochemistry, pharmacology and medical use

The effect of oral protease administration in the rat remnant kidney model

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