Triple-negative breast cancer (TNBC) lacks estrogen, progesterone, and human epidermal growth factor receptors and has a poor prognosis as it is resistant to chemotherapy. A new treatment option for t Show more
Triple-negative breast cancer (TNBC) lacks estrogen, progesterone, and human epidermal growth factor receptors and has a poor prognosis as it is resistant to chemotherapy. A new treatment option for this type of cancer may be by putting these malignant cells into dormancy. The oocyte's embryonic milieu presents a unique tumor reversion microenvironment by inducing growth arrest and changing cells' phenotypes. We conducted an in-silico study to determine the most likely oocyte extract (OE) proteins involved in inducing dormancy using HDock, CluPro, and molecular dynamic (MD) simulation. Results showed low energy scores for complexes between OE proteins and four surface markers: K1C14, CLD3, CLD4, and ITA6. Apolipoprotein A1 (APOA1) and Apolipoprotein C3 (APOC3) showed the highest stability and affinity with these four surface markers: K1C14, CLD3, CLD4, and ITA6. These proteins are involved in key tumor-related pathways such as angiogenesis, proliferation, apoptosis, and migration. This will pave the way for exploring novel therapeutic options to induce dormancy in TNBC cells. Show less
Hyperlipidemia is a known cause of coronary vascular diseases, which is a major cause of death in many parts of the world. Targeting several pathways that lead to increase in lipid profiles is of grea Show more
Hyperlipidemia is a known cause of coronary vascular diseases, which is a major cause of death in many parts of the world. Targeting several pathways that lead to increase in lipid profiles is of great potential to control diseases. 1H-indole-2-carboxamide derivatives were tested for their hypolipidemic activity at the molecular level in comparison with bezafibrate. The gene expression profiles of lipoprotein signaling and cholesterol metabolism and fatty acid metabolism PCR arrays were determined in rats with acute hyperlipidemia induced by Triton WR1339. Lipid profiles of serum from treated rats showed significant hypolipidemic effect by the compounds. Several genes of potential interest were reported to be overexpressed by Triton WR1339 including Apoc3, Apob, Hmgcs2, Apoa1, Apoe, Apof, acsl1, and Decr1. Most of the overexpressed genes were downregulated by N-(3-Benzoylphenyl)-1H-Indole-2-Carboxamide with significant decreases in Apoc3, Apob, Acaa2, Acsl1, and Slc247a5 gene expression levels. N-(4-Benzoylphenyl)-1H-Indole-2-Carboxamide and bezafibrate did not significantly affect the gene expression levels which were increased with acute hyperlipidemia induced by Triton WR1339. In conclusion, gene expression profiling identified the possible mechanism in which Triton WR1339 induces its acute hyperlipidemic effect which was reversed by the use of N-(3-Benzoylphenyl)-1H-Indole-2-Carboxamide. Show less