J Appl Biomed 12:39-47, 2014 | DOI: 10.1016/j.jab.2012.11.001

Proenzyme therapy of sarcoma S-180 and melanoma B16-F10

Pavlína Kaiserová^a, Lucie Kalferstová^a, Hana Maršíková^a, Irena Bartoňová^a, Peter Koník^b, Jan Kopecký^a, Jan Ženka^a,*

^a Department of Medical Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic

^b Laboratory of Structural Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic

The aim of this study was to evaluate the effectiveness of individual (inactive) proenzymes and mixtures thereof in cancer treatment and to compare this treatment with more frequently used therapy based on active proteases. Experiments focused on explanation of possible mechanisms of proenzyme action against tumours are included.
Proenzyme therapy of sarcoma S-180 significantly reduced tumour growth and prolonged survival of mice. The effect of trypsinogen and chymotrypsinogen was synergistic. Proenzyme therapy of melanoma B16-F10 bearing mice reduced both tumour growth and prevalence of metastases. Active enzyme based therapy of melanoma B16-F10 was less effective. Severe combined immunodeficiency (SCID) mice bearing sarcoma S-180 did not respond to the proenzyme therapy, indicating that the effect of this therapy is dependent on fully developed acquired immunity. Measured decreased levels of TGF-β and an increased amount of alpha-2 macroglobulin in serum contributed to the elucidation of the cancer treatment mechanism.
Proenzyme therapy based on administration of a mixture of trypsinogen and chymotrypsinogen is effective in cancer treatment.

Keywords: Proenzyme therapy; Proteases; Sarcoma; Melanoma; Cancer therapy

Received: October 9, 2012; Revised: November 24, 2012; Accepted: November 24, 2012; Published: January 1, 2014  Show citation