Oxidative stress is an important contributor to
cancer development. Consistent with that,
antioxidant enzymes have been demonstrated to suppress
tumorigenesis when being elevated both in vitro and in vivo, making induction of these
enzymes a more potent approach for
cancer prevention.
Protandim, a well-defined combination of widely studied medicinal plants, has been shown to induce
superoxide dismutase (SOD) and
catalase activities and reduce
superoxide generation and lipid peroxidation in healthy human subjects. To investigate whether
Protandim can suppress
tumor formation by a dietary approach, a two-stage mouse skin
carcinogenesis study was performed. At the end of the study, the mice on a
Protandim-containing basal diet had similar
body weight compared with those on the basal diet, which indicated no overt toxicity by
Protandim. After three weeks on the diets, there was a significant increase in the expression levels of SOD and
catalase, in addition to the increases in SOD activities. Importantly, at the end of the
carcinogenesis study, both skin
tumor incidence and multiplicity were reduced in the mice on the
Protandim diet by 33% and 57% respectively, compared with those on basal diet. Biochemical and histological studies revealed that the
Protandim diet suppressed
tumor promoter-induced oxidative stress (evidenced by reduction of
protein carbonyl levels), cell proliferation (evidenced by reduction of skin
hyperplasia and suppression of PKC/JNK/Jun pathway), and
inflammation (evidenced by reduction of ICAM-1/VCAM-1 expression,
NF-kappaB binding activity, and nuclear p65/p50 levels). Overall, induction of
antioxidant enzymes by
Protandim may serve as a practical and potent approach for
cancer prevention.