Invitro and Animal Studies

Most of the in-vitro and animal studies conducted on bromelain and polyenzyme therapies focused on their effects on immune function and/or inflammation; these were discussed in Chapter 12. The evidence indicates that immune modulation and anti-inflammatory effects may account for a large part of any anticancer effects seen in animals or humans.

Only three in-vitro studies have investigated the direct effects of bromelain on cancer cells. One study reported that bromelain (at 5 to 8 pM) inhibited the proliferation of mouse lymphoma, lung, and ascites tumor cells.219 The effects appeared due to the peroxidase activity of bromelain. (Peroxidases are enzymes that catalyze the conversion of hydrogen peroxide to water.) The second study reported bromelain induced differentiation in leu-

kemic cells, probably due to its ability to alter cytokine synthesis, which again points to the role of bromelain in immune modula-tion.197 In the third, a combination of bromelain and trypsin stimulated the proliferation of Ehrlich ascites tumor cells.220 This finding may not be relevant to in-vivo conditions during enzyme therapy, however.

Four animal studies examined the antitumor effects of bromelain or polyenzymes. In two of the studies, oral administration of 140 to 400 mg/kg bromelain (about 1.3 to 3.8 grams per day, as scaled to humans) inhibited metastasis of lung cancer cells in mice.207'208 In the other two, rectal administration of 45 mg/kg two times per day of a polyenzyme formula (WOBE-MUGOS) reduced metastasis and increased survival of mice with transplanted melanoma and lung cancer cells.210,221 Doses were rectally given to improve absorption. The equivalent human dose is roughly 870 milligrams per day.

Oral enzyme therapy may inhibit cancer progression or improve the effects of chemotherapy drugs through a number of mechanisms. The potential anticancer activities of bromelain are listed in Table 18.5. Although the focus is on bromelain, other proteolytic enzymes are likely to share similar characteristics. All activities except for the ability of proteolytic enzymes to increase drug absorption have been discussed in previous chapters.

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