Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
Drugs
Erschienen in: Drugs 4/2000

01.04.2000 | Review Article

Systemic Enzyme Therapy in Oncology

Effect and Mode of Action

verfasst von: Dr Jörg Leipner, Reinhard Saller

Erschienen in: Drugs | Ausgabe 4/2000

Einloggen, um Zugang zu erhalten

Abstract

Plant extracts with a high content of proteolytic enzymes have been used for a long time in traditional medicine. Besides proteolytic enzymes from plants, ‘modern’ enzyme therapy additionally includes pancreatic enzymes. The therapeutic use of proteolytic enzymes is partly based on scientific studies and is partly empirical. The aim of the current review is to provide an overview of clinical trials of systemic enzyme therapy in oncology, and to discuss the evidence for their possible mechanisms of action.
Clinical studies of the use of proteolytic enzymes in oncology have mostly been carried out on an enzyme preparation consisting of a combination of papain, trypsin and chymotrypsin. This review of these studies showed that enzyme therapy can reduce the adverse effects caused by radiotherapy and chemotherapy. There is also evidence that, in some types of tumours, survival may be prolonged.
The beneficial effect of systemic enzyme therapy seems to be based on its anti-inflammatory potential. However, the precise mechanism of action of systemic enzyme therapy remains unsolved. The ratio of proteinases to antiproteinases, which is increasingly being used as a prognostic marker in oncology, appears to be influenced by the oral administration of proteolytic enzymes, probably via an induction of the synthesis of antiproteinases. Furthermore, there are numerous alterations of cytokine composition during therapy with orally administered enzymes, which might be an indication of the efficacy of enzyme therapy. Effects on adhesion molecules and on antioxidative metabolism are also reviewed.
Literatur
1.
Vanhoof G, Cooreman W. Bromelain. In: Lauwers A, Scharpé S, editors. Pharmaceutical enzymes. New York: Marcel Dekker, 1997: 131–53
2.
De Feo V. Medicinal and magical plants in the northern Peruvian Andes. Fitoterapia 1992; 53: 417–40
3.
Rawlings ND, Barrett AJ. Evolutionary families of peptidases. Biochem J 1993; 290: 205–18PubMed
4.
Rowan AD, Buttle DJ, Barrett AJ. The cysteine proteinases of the pineapple plant. Biochem J 1990; 266: 869–75PubMed
5.
Harrach T, Eckert K, Schulze-Forster K, et al. Isolation and partial characterization of basic proteinases from stem bromelain. J Protein Chem 1995; 14: 41–52PubMedCrossRef
6.
Wrbka E, Kodras B. Unterstutzung der Chemotherapie inoperabler bronchopulmonaler Karzinome durch proteolytische Fermente. Wien Med Wochenschr 1978; 128: 153–8PubMed
7.
Kim J-P, Wa WS, Kim SJ. Effect of rosette forming T-lymphocyte level in immunochemotherapy using Picibanil and Wobe-Mugos in gastric cancer patients. Leipner J [translation (data on file)]
8.
Schedler M, Lind A, Schatzle W, et al. Adjuvant therapy with hydrolytic enzymes in oncology: a hopeful effort to avoid bleomycin induced pneumotoxicity [abstract]? J Cancer Res Clin Oncol 1980; 116: 697
9.
Lahousen M. Modification of liver parameters by adjuvant administration of proteolytic enzymes following chemotherapy in patients with ovarian carcinoma [in German]. Wien Med Wochenschr 1995; 145: 663–8PubMed
10.
Sakalova A, Dedik L, Gazova S, et al. Survival analysis of an adjuvant therapy with oral enzymes in multiple myeloma patients [abstract]. Br J Haematol 1998; 102: 353
11.
Popiela T. Wobe-Mugos E® as additive therapy after surgical treatment of colon cancer patients in combination with chemotherapy. Gerestried, Germany: MUCOS Pharma GmbH & Co., 1999 (data on file)
12.
Sebti SM, Mignano JE, Jani JP, et al. Bleomycin hydrolase: molecular cloning, sequencing, and biochemical studies reveal membership in the cysteine proteinase family. Biochemistry 1989; 28: 6544–8PubMedCrossRef
13.
Schwartz DR, Homanics GE, Hoyt DG, et al. The neutral cysteine protease bleomycin hydrolase is essential for epidermal integrity and bleomycin resistance. Proc Natl Acad Sci U S A 1999; 96: 4680–5PubMedCrossRef
14.
Kesztele V, Hürbe E, Wischin W. Erfahrung mit proteolytischen Enzymen beim Bronchuskarzinom. Wien Med Wochenschr 1976; 25-27: 412–4
15.
Beaufort F. Reduzierung von Strahlennebenwirkungen durch hydrolytische enzyme. Therapeutikon 1990; 4: 577–80
16.
Vinzenz K, Stauder U. Die therapie der radiogenen mukositis mit enzymen. In: Vinzenz K, Waclawicek HW, editors. Chirurgische therapie von kopf-hals-karzinomen. Berlin: Springer-Verlag, 1992: 300–14CrossRef
17.
Gujral MS, Patnaik PM. Efficacy and safety of Wobe-Mugos E® in preventing side-effects of radiation therapy in patients with head and neck cancer — Gerestried, Germany: MUCOS Pharma GmbH & Co, 1998 (data on file)
18.
Dale P. Efficacy and tolerance of Wobe-Mugos E® in reducing side-effects of radiation therapy in locally advanced cervical cancer — Gerestried, Germany: MUCOS Pharma GmbH & Co, 1998 (data on file)
19.
Latha B, Ramakrishnan KM, Jayaraman V, et al. Action of trypsin: chymotrypsin (Chymoral forte DS) preparation on acute-phase proteins following burn injury in humans. Burns 1997; 23 Suppl. 1: 3–7CrossRef
20.
Latha B, Ramakrishnan M, Jayaraman V, et al. Serum enzymatic changes modulated using trypsin: chymotrypsin preparation during burn wounds in humans. Burns 1997; 23: 560–4PubMedCrossRef
21.
Wood GR, Ziska T, Morgenstern E, et al. Sequential effects of an oral enzyme combination with rutoside in different in vitro and in vivo models of inflammation. Int J Immunother 1997; 13: 139–46
22.
Stauder G, Pollinger W, Fruth C. Systemic enzyme therapy: an overview of new clinical studies [German]. Allgemeinmedizin 1990; 19: 188–91
23.
Gettins P, Patston PA, Olson ST. Serpins: structure, function and biology. Heidelberg: Springer-Verlag, 1996
24.
Fisher JD, Weeks RL, Curry WM, et al. Effects of an oral enzyme preparation, Chymoral®, upon serum proteins associated with injury (acute phase reactants) in man. J Med 1974; 5: 258–73PubMed
25.
Foekens JA, Look MP, Bolt-de Vries J, et al. Cathepsin-D in primary breast cancer: prognostic evaluation involving 2810 patients. Br J Cancer 1999; 79: 300–7PubMedCrossRef
26.
27.
Pemberton PA. The role of serpin superfamily members in cancer. Cancer J 1997; 10: 24–30
28.
Joslin G, Wittwer A, Adams S, et al. Cross-competition for binding of α1-antitrypsin (α1 AT)-elastase complexes to the serpin-enzyme complex receptor by other serpin-enzyme complexes and by proteolytically modified α1 AT. J Biol Chem 1993; 268: 1886–93PubMed
29.
Olson ST, Bock PE, Kvassman J, et al. Role of the catalytic serine in the interactions of serine proteinases with protein inhibitors of the serpin family. J Biol Chem 1995; 270: 30007–17PubMedCrossRef
30.
Lah TT, Kos J. Cyteine proteinases in cancer progression and their clinical relevance for prognosis. Biol Chem 1998; 379: 125–30PubMed
31.
32.
Lah TT, Kokalj-Kunovar M, Strukelj B, et al. Stefins and lysosomal cathepsins B, L and D in human breast carcinoma. Int J Cancer 1992; 50: 36–44PubMedCrossRef
33.
Batkin S, Taussig SJ, Szekerezes J. Antimetastatic effect of bromelain with or without its proteolytic and anticoagulant activity. J Cancer Res Clin Oncol 1988; 114: 507–8PubMedCrossRef
34.
Batkin S, Taussig S, Szekerczes J. Modulation of pulmonary metastasis (Lewis lung carcinoma) by bromelain, an extract of the pineapple stem (Ananas comosus). Cancer Invest 1988; 6: 241–2PubMedCrossRef
35.
Taussig SJ, Szekerezes J, Batkin S. Inhibition of tumor growth in vitro by bromelain, an extract of the pineapple plant (Ananas comosus). Planta Medica 1985; 51: 538–9PubMedCrossRef
36.
Bellelli A, Mattioni M, Rusconi V, et al. Inhibition of tumor growth, invasion and metastasis in Papain-immunized mice. Invasion Metastasis 1990; 10: 142–69PubMed
37.
Mazourov VI, Lila AM, Klimko NN, et al. The efficacy of systemic enzyme therapy in the treatment of rheumatoid arthritis. Int J Immunother 1997; 13: 85–92
38.
Lackovic V, Rovensky J, Horvathová M, et al. Interferon production in whole blood cultures from volunteers and rheumatoid arthritis patients after medication with oral enzymes. Int J Immunother 1997; 13: 159–66
39.
Baenkler H-W. Medizinische Immunologie: Grundlagen, Diagnostik, Klinik, Therapie, Prophylaxe, Sonderbereiche. Landsberg am Lech, Germany: Ecomed, 1995
40.
Desser L, Rehberger A, Kokron E, et al. Cytokine synthesis in human peripheral blood mononuclear cells after oral administration of polyenzyme preparations. Oncology 1993; 50: 403–7PubMedCrossRef
41.
42.
James K. Interactions between cytokines and α2-macroglobulin. Immunol Today 1990; 11: 163–6PubMedCrossRef
43.
Borth W. α2-Macroglobulin, a multifunctional binding protein with targeting characteristics. FASEB J 1992; 6: 3345–53PubMed
44.
Borth W, Dunky A, Kleesiek K. α2-Macroglobulin-proteinase complexes as correlated with α1-proteinase inhibitor-elastase complexes in synovial fluids of rheumatoid arthritis patients. Arthritis Rheum 1986; 29: 319–25PubMedCrossRef
45.
Harrach T, Gebauer F, Eckert K, et al. Bromelain proteinases modulate the CD44 expression on human Molt 4/8 leukemia and SK-Mel 28 melanoma cells in vitro. Int J Oncol 1994; 5: 485–8PubMed
46.
Gebauer F, Micheel B, Stauder G, et al. Proteolytic enzymes modulate the adhesion molecule CD44 on malignant cells in vitro. Int J Immunother 1997; 13: 111–9
47.
Grabowska E, Eckert K, Fichtner I, et al. Bromelain proteases suppress growth, invasion and lung metastasis of B16F10 mouse melanoma cells. Int J Oncol 1997; 11: 243–8PubMed
48.
Targoni OS, Tary-Lehmann M, Lehmann PV. Prevention of mutine EAE by oral hydrolytic enzyme treatment. J Autoimmun 1999; 12: 191–8PubMedCrossRef
49.
Sakalova A, Kunze R, Holomanova D, et al. Density of adhesive proteins after oral administration of proteolytic enzymes in multiple myeloma [in Slovak]. Vnitr Lek 1995; 41: 822–6PubMed
50.
Strobel T, Swanson L, Cannistra CA. In vivo inhibition of CD44 limits intra-abdominal spread of a human ovarian cancer xenograft in nude mice: a novel role for CD44 in the process of peritoneal implantation. Cancer Res 1997; 57: 1228–32PubMed
51.
Zawadzki V, Perschl A, Rosel M, et al. Blockade of metastasis formation by CD44-receptor globulin. Int J Cancer 1998; 75: 919–24PubMedCrossRef
52.
Zavadová E, Desser L, Mohr T. Stimulation of reactive oxygen species production and cytotoxicity in human neutrophils in vitro and after oral administration of a polyenzyme preparation. Cancer Biother 1995; 10: 147–52PubMedCrossRef
53.
Latha B, Ramakrishnan M, Jayaraman V, et al. The efficacy of trypsin: chymotrypsin preparation in the reduction of oxidative damage during burn injury. Burns 1998; 24: 532–8PubMedCrossRef
54.
Netti C, Bandi GL, Pecile A. Anti-inflammatory action of proteolytic enzymes of animal vegetable or bacterial origin administered orally compared with that of known anti-phlogistic compounds. Farmaco — Edizione Pratica 1972; 27: 453–66PubMed
55.
Ito C, Yamaguchi K, Shibutani Y, et al. Anti-inflammatory actions of proteases, bromelain, trypsin and their mixed preparation. Folia Pharmacol Japan 1979; 75: 227–37CrossRef
Metadaten
Titel
Systemic Enzyme Therapy in Oncology
Effect and Mode of Action
verfasst von
Dr Jörg Leipner
Reinhard Saller
Publikationsdatum
01.04.2000
Verlag
Springer International Publishing
Erschienen in
Drugs / Ausgabe 4/2000
Print ISSN: 0012-6667
Elektronische ISSN: 1179-1950
DOI
https://doi.org/10.2165/00003495-200059040-00004

Weitere Artikel der Ausgabe 4/2000

Drugs 4/2000 Zur Ausgabe

Review Article

Tyrosine Kinase Inhibitors Targeted to the Epidermal Growth Factor Receptor Subfamily

Adis Drug Evaluation

Bupropion

Leading Article

Role of Tumour Necrosis Factor-α in the Progression of Heart Failure

Adis Drug Evaluation

Montelukast

Adis New Drug Profile

Linezolid

Adis New Drug Profile

Racecadotril