Abstract
BackgroundEstrogen sulfotransferase catalyzes conjugation of sulfuryl-group to estradiol/estrone and regulates E2 availability/activity via estrogen-receptor or non-receptor mediated pathways. Sulfoconjugated estrogen fails to bind estrogen-receptor (ER). High estrogen is a known carcinogen in postmenopausal women. Reports reveal a potential redox-regulation of hSULT1E1/E2-signalling. Further, oxidatively-regulated nuclear-receptor-factor 2 (Nrf2) and NFκβ in relation to hSULT1E1/E2 could be therapeutic-target via cellular redox-modification.MethodsHere, oxidative stress-regulated SULT1E1-expression was analyzed in human breast carcinoma-tissues and in rat xenografted with human breast-tumor. Tumor and its surrounding tissues were obtained from the district-hospital. Intracellular redox-environment of tumors was screened with some in vitro studies. RT-PCR and western blotting was done for SULT1E1 expression. Immunohistochemistry was performed to analyze SULT1E1/Nrf2/NFκβ localization. Tissue-histoarchitecture/DNA-stability (comet assay) studies were done.ResultsOxidative-stress induces SULT1E1 via Nrf2/NFκβ cooperatively in tumor-pathogenesis to maintain the required proliferative-state under enriched E2-environment. Higher malondialdehyde/non-protein-soluble-thiol with increased superoxide-dismutase/glutathione-peroxidase/catalase activities was noticed. SULT1E1 expression and E2-level were increased in tumor-tissue compared to their corresponding surrounding-tissues.ConclusionsIt may be concluded that tumors maintain a sustainable oxidative-stress through impaired antioxidants as compared to the surrounding. Liver-tissues from xenografted rat manifested similar E2/antioxidant dysregulations favoring pre-tumorogenic environment.
Highlights
Estrogen sulfotransferase catalyzes conjugation of sulfuryl-group to estradiol/estrone and regulates E2 availability/activity via estrogen-receptor or non-receptor mediated pathways
Oxidative stress markers suggests higher free radical burden in the tumor tissue The mean non‐protein soluble thiol (NPSH) level in the surrounding and the tumor tissue was not significantly increased in terms of protein, Estradiol level in tumor tissue compared to its surrounding tissue The average estradiol was found to be higher in the tumor as compared to its corresponding surrounding with mean values 108.27 ρg (± 13.05) in the surrounding it was 209 pg (± 33.14) in the tumor tissues (Fig. 1)
Alterations in the activities of antioxidant enzymes in the tumor tissue The antioxidant enzyme superoxide dismutase (SOD) activity was found to be higher in the tumor as compared to its surrounding (Fig. 2, SOD1)
Summary
Estrogen sulfotransferase catalyzes conjugation of sulfuryl-group to estradiol/estrone and regulates E2 availability/activity via estrogen-receptor or non-receptor mediated pathways. Reports reveal a potential redox-regulation of hSULT1E1/E2-signalling. Oxidatively-regulated nuclear-receptor-factor 2 (Nrf2) and NFκβ in relation to hSULT1E1/E2 could be therapeutic-target via cellular redox-modification. Breast cancer is one of the most devastating and common cancers in women worldwide [1]. The global occurrence rate of breast cancer depends on the locations and geographical variations [2]. In the year 2008, 8 million deaths were recorded as a result of malignant breast cancers, and that figure is assumed to be 11 million by 2030 [4]. With the increasing of average life-span in developed countries, the incidence of this disease among older people is increasing [5]. Resources and health beneficiaries are one of the major factors of the disease incidence and mortality.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
