Inhibition of progesterone (P4) synthesis by cumulus cells during bovine in vitro oocyte maturation (IVM) causes a decrease in subsequent embryo development, indicating that P4 intracellular signaling within the cumulus oocyte complex (COC) is important for oocyte developmental competence. The aim of the present study was to further elucidate, on a protein level, the downstream signaling pathway involved in P4 regulation of oocyte developmental competence. COCs were subjected to IVM for 24 h in the presence or absence of trilostane, aglepristone, or promegestone (R5020). These altered IVM conditions resulted in dynamic changes in protein expression of the progesterone receptors and the cell death-regulated proteins AVEN, BCL-xL, and active caspase 3. In addition, AVEN protein localization, caspase 3 activation, and mitochondrial distribution were studied by immunofluorescence. Inhibition of progesterone synthesis (trilostane treatment) resulted in changes in AVEN localization within the COC, corresponding to caspase 3 activation and altered mitochondrial distribution. AVEN was also found to bind BCL-xL in COCs, but this interaction was lost following treatment with trilostane.
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http://dx.doi.org/10.1095/biolreprod.113.111880 | DOI Listing |
Bioorg Chem
January 2025
Department of In Vitro Carcinogenesis and Cellular Chemotherapy, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata 700026, India. Electronic address:
Histone deacetylases (HDACs) play a critical role in chromatin remodelling and modulating the activity of various histone proteins. Aberrant HDAC functions has been related to the progression of breast cancer (BC), making HDAC inhibitors (HDACi) promising small-molecule therapeutics for its treatment. Hydroxamic acid (HA) is a significant pharmacophore due to its strong metal-chelating ability, HDAC inhibition properties, MMP inhibition abilities, and more.
View Article and Find Full Text PDFPharmaceuticals (Basel)
January 2025
School of Pharmacy and Pharmaceutical Sciences, Panoz Institute, Trinity College Dublin, D02 PN40 Dublin, Ireland.
The synthesis of ()-1-(1,3-diphenylallyl)-1-1,2,4-triazoles and related compounds as anti-mitotic agents with activity in breast cancer was investigated. These compounds were designed as hybrids of the microtubule-targeting chalcones, indanones, and the aromatase inhibitor letrozole. : A panel of 29 compounds was synthesized and examined by a preliminary screening in estrogen receptor (ER) and progesterone receptor (PR)-positive MCF-7 breast cancer cells together with cell cycle analysis and tubulin polymerization inhibition.
View Article and Find Full Text PDFBMC Complement Med Ther
January 2025
Laser Research Centre, Faculty of Health Sciences, Doornfontein Campus, University of Johannesburg, Johannesburg, 2028, South Africa.
Background: Amongst all neoplastic diseases, breast cancer represents a major cause of death among the female population in developed and developing countries. Since alkaloid drugs are commonly used in chemotherapy to manage this disease, this study investigated the anti-proliferative effectiveness of alkaloid-rich fractions of Senna didymobotrya leaves only and with laser irradiation against MCF-7 breast cancer cells.
Method And Materials: A powdered sample of the plant leaves was extracted with 50% ethanol, filtered and their pH was adjusted with acid and base solution followed by partitioning with chloroform and ethyl acetate solvents.
Sci Rep
January 2025
Laboratory of Hormonal Carcinogenesis, IBYME-CONICET, Ciudad Autónoma de Buenos Aires (CABA), V. Obligado 2490, C1428ADN, Buenos Aires, Argentina.
Breast cancer (BC) patient-derived xenografts (PDX) are relevant models for precision medicine. However, there are no collections derived from South American BC patients. Since ethnicity significantly impacts clinical outcomes, it is necessary to develop PDX models from different lineages.
View Article and Find Full Text PDFAdv Exp Med Biol
January 2025
Molecular Oncology, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
RANK pathway has attracted increasing interest as a promising target in breast cancer, given the availability of denosumab, an anti-RANKL drug. RANK signaling mediates progesterone-driven regulation of mammary gland development and favors breast cancer initiation by controlling mammary cell proliferation and stem cell fate. RANK activation promotes luminal mammary epithelial cell senescence, acting as an initial barrier to tumorigenesis but ultimately facilitating tumor progression and metastasis.
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