Abstract
Protandim, a well defined dietary combination of 5 well-established medicinal plants, is known to induce endogenous antioxidant enzymes, such as manganese superoxide dismutase (MnSOD). Our previous studies have shown through the induction of various antioxidant enzymes, products of oxidative damage can be decreased. In addition, we have shown that tumor multiplicity and incidence can be decreased through the dietary administration of Protandim in the two-stage skin carcinogenesis mouse model. It has been demonstrated that cell proliferation is accommodated by cell death during DMBA/TPA treatment in the two-stage skin carcinogenesis model. Therefore, we investigated the effects of the Protandim diet on apoptosis; and proposed a novel mechanism of chemoprevention utilized by the Protandim dietary combination. Interestingly, Protandim suppressed DMBA/TPA induced cutaneous apoptosis. Recently, more attention has been focused on transcription-independent mechanisms of the tumor suppressor, p53, that mediate apoptosis. It is known that cytoplasmic p53 rapidly translocates to the mitochondria in response to pro-apoptotic stress. Our results showed that Protandim suppressed the mitochondrial translocation of p53 and mitochondrial outer membrane proteins such as Bax. We examined the levels of p53 and MnSOD expression/activity in murine skin JB6 promotion sensitive (P+) and promotion-resistant (P-) epidermal cells. Interestingly, p53 was induced only in P+ cells, not P- cells; whereas MnSOD is highly expressed in P- cells when compared to P+ cells. In addition, wild-type p53 was transfected into JB6 P- cells. We found that the introduction of wild-type p53 promoted transformation in JB6 P- cells. Our results suggest that suppression of p53 and induction of MnSOD may play an important role in the tumor suppressive activity of Protandim.
Highlights
Apoptosis is an intricate pathway triggered by various sources, such as genotoxic stress, DNA damage, cytotoxicity and irradiation
We investigated the effects of Protandim on cutaneous apoptosis, p53 mitochondrial translocation and compared the p53 and manganese superoxide dismutase (MnSOD) status between promotable and non-promotable skin epidermal cells
Since DMBA/TPA causes cell death, we investigated the effects of Protandim on cutaneous apoptosis
Summary
Apoptosis is an intricate pathway triggered by various sources, such as genotoxic stress, DNA damage, cytotoxicity and irradiation. During DMBA/TPA treatment, both tumor suppressor gene and oncogene activation occur simultaneously leading to downstream oxidative stress propagation. The reduction of antioxidant activity contributes to oxidative stress propagation which leads to downstream cancer development. It is known that various dietary components can induce endogenous antioxidant enzymes We have demonstrated this same paradigm with the use of Protandim, a dietary combination of five extensively studied medicinal plants, given via dietary administration [9]. The Protandim diet exhibited its anti-carcinogenic activity by reducing tumor incidence and multiplicity via modulating oxidative stress through the induction of endogenous antioxidant enzymes [9]. We investigated the effects of Protandim on cutaneous apoptosis, p53 mitochondrial translocation and compared the p53 and MnSOD status between promotable and non-promotable skin epidermal cells
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