An experimental study has been conducted to investigate the efficacy of geraniol (GNL) isolated from lemomgrass in protecting against cardiac toxicity induced by tilmicosin (TIL) in albino mice. Compared to TIL-treated mice, those supplemented with GNL had a thicker left ventricular wall and a smaller ventricular cavity. Studies of TIL animals treated with GNL showed that their cardiomyocytes had markedly changed in diameter and volume, along with a reduction in numerical density. After TIL induction, animals showed a significant increase in the protein expression of TGF-ß1, TNF-α, nuclear factor kappa B (NF-kB), by 81.81, 73.75 and 66.67%, respectively, and hypertrophy marker proteins ANP, BNP, and calcineurin with respective percentages of 40, 33.34 and 42.34%. Interestingly, GNL significantly decreased the TGF-ß1, TNF-α, NF-kB, ANP, BNP, and calcineurin levels by 60.94, 65.13, 52.37, 49.73, 44.18 and 36.84%, respectively. As observed from histopathology and Masson's trichrome staining, supplementation with GNL could rescue TIL-induced cardiac hypertrophy. According to these results, GNL may protect the heart by reducing hypertrophy in mice and modulating biomarkers of fibrosis and apoptosis.
Acyclic Monoterpenes , Cymbopogon , Tylosin/analogs & derivatives , Mice , Animals , NF-kappa B/metabolism , Transforming Growth Factor beta1/metabolism , Transforming Growth Factor beta1/pharmacology , Tumor Necrosis Factor-alpha/metabolism , Calcineurin/metabolism , Calcineurin/pharmacology , Oxidative Stress , Myocytes, Cardiac , Cardiomegaly/metabolism , Cardiomegaly/pathology
Breast cancer is the major type among the women population globally. The treatment of cancer metastasis has made modest progress due to multiple factors. Thidiazuron (TDZ) is a novel plant growth regulator that has been shown to have anticancer effects. Therefore, we explored the anti-metastatic potentials of TDZ in cell lines by assessing its potential to suppress the epithelial-mesenchymal transition (EMT). We pretreated the BEAS-2B and breast cancer (MDA-MB-231) cells with TDZ and deliberated alteration in a cell viability, mammosphere, migration, NF-кB signalling, PI3K/AKT signalling and matrix metalloproteinase (MMP) expression and analysed the EMT induction by TGF-ß/TNF-α-stimulated BEAS-2B cells. Treatment with TDZ (5-50 µmol) diminished the migration and invasion of the extremely metastatic MDA-MB-231 cells. Additionally, TDZ treatment led to down-regulation of uPAR, uPA, VEGF and MMP-2/-9 expression and up-regulation of TIMP-1/2 expression in these cells. Furthermore, TDZ treatment blocked invasion and EMT in non-tumorigenic BEAS-2B epithelial cells stimulated with TGF-ß/TNF-α.TDZ prevents EMT and may thus block metastasis of breast cancer cells.
Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Epithelial-Mesenchymal Transition/drug effects , NF-kappa B/metabolism , Phenylurea Compounds/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects , Thiadiazoles/pharmacology , Biomarkers , Caspase 3/metabolism , Cell Line, Tumor , Cell Movement , Cell Survival/drug effects , DNA Fragmentation , Female , Humans , Immunohistochemistry , Matrix Metalloproteinases/metabolism , Poly(ADP-ribose) Polymerases/metabolism , Protein Binding