Department of Pharmacology, Toxicology and Neuroscience, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States of America.
PLoS One. 2010 Jul 30;5(7):e11902. doi: 10.1371/journal.pone.0011902.
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.
Protandim，一种由 5 种已确立的药用植物组成的明确的饮食组合，已知可诱导内源性抗氧化酶，如锰超氧化物歧化酶（MnSOD）。我们之前的研究表明，通过诱导各种抗氧化酶，可以减少氧化损伤产物。此外，我们已经表明，通过在二阶段皮肤致癌小鼠模型中饮食给予 Protandim，可以减少肿瘤多发性和发生率。已经证明，在二阶段皮肤致癌模型中，DMBA/TPA 处理会通过细胞死亡来适应细胞增殖。因此，我们研究了 Protandim 饮食对细胞凋亡的影响；并提出了 Protandim 饮食组合所利用的化学预防的新机制。有趣的是，Protandim 抑制了 DMBA/TPA 诱导的皮肤细胞凋亡。最近，人们越来越关注肿瘤抑制因子 p53 的转录独立机制，该机制介导细胞凋亡。已知细胞质 p53 会迅速响应促凋亡应激而向线粒体转移。我们的结果表明，Protandim 抑制了 p53 和 Bax 等线粒体外膜蛋白的线粒体易位。我们检查了 p53 和 MnSOD 在小鼠皮肤 JB6 促进敏感（P+）和促进抗性（P-）表皮细胞中的表达/活性水平。有趣的是，p53 仅在 P+细胞中诱导，而不在 P-细胞中诱导；而 MnSOD 在 P-细胞中的表达水平高于 P+细胞。此外，将野生型 p53 转染到 JB6 P-细胞中。我们发现，野生型 p53 的引入促进了 JB6 P-细胞的转化。我们的结果表明，p53 的抑制和 MnSOD 的诱导可能在 Protandim 的肿瘤抑制活性中发挥重要作用。
