Publications by authors named "Victoria L Greenberg"
Objectives: To determine if SAHA, a histone deacetylase inhibitor, decreases ovarian cancer cell viability when combined with paclitaxel in vitro, and to explore molecular alterations of combined paclitaxel+SAHA treatment.
Methods: SKOV3 and Hey ovarian cancer cell lines were treated for 24 h with paclitaxel, then re-treated with SAHA or paclitaxel for an additional 48 h. Protein extracts were prepared at 48 h for western blot analysis.
Article Synopsis
- The study aimed to evaluate the effects of the drug suberoylanilide hydroxamic acid (SAHA) alone and in combination with paclitaxel on ovarian cancer cells and in a mouse model.
- Results showed that while both SAHA and paclitaxel reduced cancer cell viability and increased apoptosis, their combination did not provide significant additional benefits; however, the order of administration affected survival rates in mice.
- Overall, the findings suggest that using SAHA alongside paclitaxel could enhance chemotherapy effectiveness in ovarian cancer, emphasizing the importance of drug sequencing in treatment.
Initial chemotherapeutic treatment triggers a stress-related response, which can lead to an increase in the expression of survival proteins. In this study we examine whether paclitaxel (PTX) alters the expression and/or phosphorylation of the translation initiation proteins, eukaryotic initiation factor 4E (eIF-4E) and 4E-binding protein (4E-BP1), a suppressor of eIF-4E in the dephosphorylated state. We found that PTX induced the hyperphosphorylation of 4E-BP1 in the breast cancer cell line, MDA MB 231, which reduced its association with eIF-4E, but did not alter the expression and phosphorylation of eIF-4E.
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- Ovarian cancer has a high mortality rate partly due to drug-resistant disease, highlighting the need for new chemotherapeutics like histone deacetylase inhibitors (HDAIs).
- In experiments, combining HDAIs with paclitaxel (PTX) effectively induced cell death in ovarian cancer cells, matching the effectiveness of continuous PTX and outperforming continuous HDAI alone.
- The order of drug administration impacted the effectiveness of the treatment, but the p53 status of the cells did not affect the outcomes, indicating HDAIs could be beneficial as an additional therapy for ovarian cancer.