Oral enzymes as additive cancer therapy

Oral therapy with proteolytic enzymes (OTPE) (papain, bromelain, trypsin, chymotrypsin amylase and lipase) has been used in additive cancer therapy for several years and has led to a reduction in adverse effects after cancer treatment (radiation and chemotherapy). OTPE has been proven to have a beneficial effect, especially in cancers and other conditions involving elevated transforming growth factor-β (TGF-β) expression. Proteases such as trypsin, chymotrypsin, bromelain and papain have been demonstrated to be capable of converting the slow form of α 2 -macroglobulin into the fast form. This form of α 2 -macroglobulin is capable of irreversibly binding TGF-β. Subsequently the TGF-β-α 2 -macroglobulin complex can be quickly removed via endocytosis. Since the production of TGF-β is regulated by an autocrine loop, removal of TGF-β results in down-regulation of TGF-β overproduction. It has been proposed that OTPE may act through this interruption of the autocrine loop. In vitro reduction in TGF-β overexpression in tumor-associated macrophages leads to enhanced tumor killing capacity as well as to stimulation of natural killer cell and granulocyte cytotoxicity In clinical trials with patients suffering from polycythemia vera or myelofibrosis, treatment with proteolytic enzymes has been shown to reduce elevated serum concentrations of TGF-β. These findings suggest that through reduction of TGF-β overproduction, OTPE could be beneficial in the inhibition of fibrosis and in additive tumor therapy.