ABSTRACT
The present study was undertaken to evaluate the chemopreventive activity of myrtenal, a natural monoterpene, against bladder carcinoma in rats induced with N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) and promoted with γ-ionizing radiation (γ-IRR) as well as to assess the involvement of inflammation, apoptosis and oxidative damage in tumor development. Histopathological examination of rat bladder revealed the presence of noninvasive papillary transitional cell carcinoma (Grade 2) in sections from BBN group indicating the credibility of the applied carcinogenesis model. Myrtenal treatment caused improvement in urinary bladder mucosa with cells more likely in Grade 1. Administration of myrtenal to BBN-treated rats exhibited downregulation in the expressions of COX-2, NF-kB and STAT-3 associated with suppression of inflammatory cytokines levels of TNF-α and IL-6 as well as biomarkers of oxidative damage (MDA & NO). In addition, myrtenal treatment caused a significant increase in caspase-3 activity and Bax/Bcl-2 ratio. Data obtained suggested that the anti-inflammatory effect and the induction of apoptosis contributed largely to the beneficial antitumor effects of myrtenal in rats with BBN/γ-IRR-induced bladder carcinoma. Present findings, in addition to benefits described in other pathologies, indicated myrtenal as a potential adjuvant natural compound for the prevention of tumor progression of bladder cancer.
Subject(s)
Nitrosamines , Urinary Bladder Neoplasms , Animals , Bicyclic Monoterpenes , Butylhydroxybutylnitrosamine/metabolism , Butylhydroxybutylnitrosamine/toxicity , Carcinogenesis , Carcinogens/pharmacology , Nitrosamines/pharmacology , Rats , Urinary Bladder/metabolism , Urinary Bladder/pathology , Urinary Bladder Neoplasms/chemically induced , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/prevention & controlABSTRACT
Background: MicroRNAs (miRs) are small (19-25 nucleotides), non-protein coding RNAs that regulate gene expression, and thus play essential roles in cell cycle progression. The evidence has demonstrated that the expression of several miRs is dysregulated in human cancer. Methods: The study includes 179 female patients and 58 healthy women Patients were identified as luminal A, B, Her-2/neu, and basal-like, as well as classified into I, II, and III stages. Analysis of the expression fold change of miR-21 and miR-34a with molecular markers, including the oncogene Bcl-2 (B-cell lymphoma 2) and the tumor suppressor genes BRCA1 (breast cancer susceptibility gene 1), BRCA2 (breast cancer susceptibility gene 2), and the tumor suppressor protein p53, was carried out for all patients, pre- and post-chemotherapy, and for all healthy women. Results: At diagnosis (pre-chemotherapy), miR-21 was up-regulated (p < 0.001), while miR-34a was down-regulated (p < 0.001). Post-chemotherapy, the expression of miR-21 decreased significantly (p < 0.001), while the expression of miR-34a increased significantly (p < 0.001). Conclusion: miR-21 and miR-34a may be helpful to non-invasive biomarkers to evaluate the response of breast cancer to chemotherapy.
Subject(s)
Breast Neoplasms , MicroRNAs , Humans , Female , MicroRNAs/genetics , Breast Neoplasms/genetics , Egypt , Oncogenes , BiomarkersABSTRACT
Radiation protection research receives intense focus due to its significant impact on human health. The present study was undertaken to investigate the protective effect of pretreatment with tomato seed oil (TSO) against gamma radiation-induced damage in rats. Male Wistar rats were divided into four groups: (1) untreated control; (2) TSO-supplemented; (3) gamma-irradiated; (4) TSO-pretreated and gamma-irradiated. Acute exposure of animals to a single gamma radiation dose (6 Gy) induced oxidative stress in major body organs, altered serum lipid homeostasis, significantly increased serum testosterone and sorbitol dehydrogenase levels, and elicited a systemic inflammation as manifested by the induction of serum vascular cell adhesion molecule-1. Oral pretreatment with TSO (1 ml/kg; 3 times/week for 8 weeks) before exposure to gamma radiation protected rats against ionizing radiation-induced oxidative stress, restored lipid homeostasis, and suppressed systemic inflammation. Histological findings of target tissues verified biochemical data. The radioprotective ability of TSO was attributed to its content of phytosterols, policosanol, and antioxidants, including lycopene, ß-carotene, lutein, and tocopherols. TSO is considered a promising radioprotective agent that can be effectively used to protect the body from the damaging effects of harmful radiation.