Tania Maheshwari
Research Mentor: Laura Kresty
Mentor Department: Section of Thoracic Surgery, Department of Surgery, Medicine
Author(s): Tania Maheshwari , Kathryn Hudack , David Ntsiful, Audrey DeUgarte , Yun Zhang , Analisa DiFeo , Laura Kresty
Session: Session 4 (1:00 PM – 1:50 PM)
Presentation Type: Poster 56
Abstract
Ovarian cancer is the leading cause of death from gynecologic malignancies, largely due to late-stage diagnosis and the development of resistance to standard chemotherapy. First-line treatment typically consists of platinum- and taxane-based agents, such as carboplatin and paclitaxel. Although many patients initially respond, only 41% achieve a complete response, and 70-80% ultimately relapse. This highlights the urgent need for new therapies and a deeper understanding of resistance mechanisms. Cranberry proanthocyanidins (C-PACs) are of interest because their unique A-type linkages and polyphenol-rich structure enable strong interactions with cellular proteins and membranes, imparting antioxidant, anti-inflammatory, and anti-cancer properties in other model systems. Our laboratory evaluated the anti-cancer properties of C-PACs in ovarian cancer cell lines, specifically in parental OV81 cells and platinum-resistant OV81-CP40 cells, with preliminary results suggesting that C-PACs act synergistically with standard-of-care chemotherapeutic agents, carboplatin and paclitaxel, to induce cell death. Building on these observations, the present mechanistic study examines the specific proteins driving treatment-induced cell death in platinum-resistant OV81-CP40 cells. Following treatment, protein lysates will be collected from OV81-CP40 cells for Western blot analysis and a panel of apoptosis-linked and epithelial-to-mesenchymal transition (EMT) markers. We will assess activation of apoptotic pathways by probing for cleaved PARP, a Caspase panel, as well as key BCL-2 family regulators. EMT makers will include ZO-1, Snail, Vimentin, and ß-Catenin. Our comprehensive assessment of apoptosis and EMT markers will reveal the mechanisms by which C-PACs sensitize ovarian cancer to chemotherapy. Future directions will include evaluating the effects of C-PACs on DNA repair and the cell cycle-related alterations in ovarian cancer.
