Abstract
Both selenium (Se) and polysaccharides from Pyracantha fortuneana (Maxim.) Li (PFPs) (P. fortuneana) have been reported to possess antioxidative and immuno-protective activities. Whether or not Se-containing polysaccharides (Se-PFPs) have synergistic effect of Se and polysaccharides on enhancing the antioxidant and immune activities remains to be determined. We previously reported that polysaccharides isolated from Se-enriched P. fortuneana (Se-PFPs) possessed hepatoprotective effects. However, it is not clear whether or not they have anti-mutagenic effects. In the present study, we compared and evaluated anti-mutagenic effects of Se-PFPs at three concentrations (1.35, 2.7 and 5.4 g/kg body weight) with those of PFPs, Se alone or Se + PFPs in mice using micronucleus assay in bone marrow and peripheral blood as well as mitomycin C-induced chromosomal aberrations in mouse testicular cells. We also elucidated the underlying mechanism. Our results demonstrated that Se-PFPs inhibited cyclophosphamide (CP)-induced micronucleus formation in both bone marrow and peripheral blood, enhanced the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in mouse liver, and reduced the activity and expression of cytochrome P450 1A (CYP4501A) in mouse liver in a dose-dependent manner. In addition, we found that the anti-mutagenic potential of Se-PFPs was higher than those of PFPs, Se alone or Se + PFPs at the same level. These results suggest that the anti-mutagenic potential of Se-PFPs may be mediated through the inhibition of the activity and expression of CYP4501A. This study indicates that application of Se-PFPs may provide an alternative strategy for cancer therapy by targeting CYP1A family.
Highlights
The genetic changes in cancer cells or the mutations of cancer-related genes, including point mutation of oncogenes and cancer suppressor genes, insertion or deletion of small DNA fragment, DNA rearrangement, copy number variation, acquisition of exogenous DNA segment, etc. have been causally associated with oncogenesis [1,2,3]
The results suggest that the inhibition of hepatic Cytochrome P450 1A (CYP1A) activity and expression is associated to anti-mutagenicity of Se-PFPs, which may provide an alternative strategy for cancer therapy by targeting the relationship between Se-PFPs and CYP1A
We found that Se-PFPs caused significantly higher inhibition on CP-induced MN formation in bone marrow, induced significantly higher activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), and caused significantly stronger inhibition on the CP-induced mutagenicity; more significantly, it down regulated the expression of mRNA and protein level of hepatic CYP1A1 and CYP1A2 as compared to those induced by PFPs and
Summary
The genetic changes in cancer cells or the mutations of cancer-related genes, including point mutation of oncogenes and cancer suppressor genes, insertion or deletion of small DNA fragment, DNA rearrangement, copy number variation, acquisition of exogenous DNA segment, etc. have been causally associated with oncogenesis [1,2,3]. Up to July 2010, the Catalogue of Somatic Mutations in Cancer (COSMIC) had described a total of 136,326 coding mutations among 541,928 tumor samples where 26% (4803/18,490) of the documented genes had at least one mutation [4]. The correlations between the mutation of 50 -untranslated region (50 -UTR), 30 -UTR region or promoter in mRNA and tumorigenesis have been documented [5,6,7]. There exist certain relationships between DNA damage/mutation and oxidative stress. The pathogenic impacts of oxidative stress are mainly mediated through chromatin alterations and cellular changes, which are the common mechanisms for those human pathologies [10,11,12,13]. Oxidative stress is a promising target for the prevention and treatment of these diseases
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