Multidrug resistance (MDR) is one of the major therapeutic challenges that limits the efficacy of chemotherapeutic response resulting in poor prognosis of ovarian cancer (OC). The multidrug resistance protein 1 (MRP1) is a membrane-bound ABC transporter involved in cross resistance to many structurally and functionally diverse classes of anticancer drugs including doxorubicin, taxane, and platinum. In this study, we utilize homology modelling and molecular docking analysis to determine the binding affinity and the potential interaction sites of MRP1 with Carboplatin, Gemcitabine, Doxorubicin, Paclitaxel, and Topotecan. We used AutoDock Vina scores to compare the binding affinities of the anticancer drugs against MRP1. Our results depicted Carboplatin < Gemcitabine < Topotecan < Doxorubicin < Paclitaxel as the order of binding affinities. Paclitaxel has shown the highest binding affinity whereas Carboplatin displayed the lowest affinity to MRP1. Interestingly, our data showed that Carboplatin, Paclitaxel, and Topotecan bind specifically to Asn510 residue in the transmembrane domains 1 of the MRP1. Our results suggest that Carboplatin could be an appropriate therapeutic choice against MRP1 in OC as it couples weakly with Carboplatin. Further, our findings also recommend opting Carboplatin with Gemcitabine as a combinatorial chemotherapeutic approach to overcome MDR phenotype associated with recurrent OC.

Background: Repressor element 1‐silencing transcription factor (REST) acts as a transcriptional repressor by recruiting several chromatin modifiers, including histone deacetylase (HDAC). Elevated REST expression in medulloblastoma has been associated with tumor progression nevertheless, the tumor shows high sensitivity to HDAC inhibitors (HDACi). However, the functional implications of REST and its requirement for HDACi‐induced anti‐cancer effects are not well understood.Methods: In this study, the expression of REST was evaluated across the medulloblastoma subgroups and subtypes using published gene expression data. Further, the expression of REST was modulated using the CRISPR/Cas9 knockout and shRNA knockdown in the Daoy medulloblastoma cell line.Results: The results of this study showed that the expression of REST is elevated in most medulloblastoma subgroups compared to the non‐cancerous cerebellum. Blocking of REST expression resulted in increasing the expression of REST‐regulated genes, a moderate decrease in the fraction of the cells in the S‐phase, and reducing the cells' migration ability. However, REST deficiency did not lead to a marked decrease in the Daoy cell viability and sensitivity to HDACi.Conclusion: The findings of this study indicate that REST is not essential for sustaining the proliferation/viability of the Daoy cells. It also revealed that the anti‐proliferative effect of HDACi is independent of REST expression.

MS‐275, a histone deacetylase inhibitor, has proven anticancer activities against various malignancies. However, its clinical application has been constrained by dose‐limiting toxicity, off‐target effects, and variable clinical outcomes. Clinical data suggest that sustained low MS‐275 doses could achieve a more selective and consistent effect. This study aimed at enhancing the anticancer activity of MS‐275 by encapsulating it in D‐α‐tocopheryl polyethylene glycol 1000 succinate (TPGS) micelles. The produced nanoformulations were characterized by their low polydispersity (0.201), negative zeta potential (−0.397 mV), and high entrapment efficiency (98.8%). Experimental evaluation of the formulation showed a significant reduction in HepG2, HCT116, and MCF7 cells’ viability, associated with enhanced apoptosis at a lower IC₅₀ compared to MS‐275 alone. The formulation was further examined on cancer cells xenografted on the chorioallantoic membrane (CAM) of chick embryos. The results showed a substantial reduction in tumor size. TPGS micelles alone induced an accumulation in G1 and slightly reduced the cellular viability of the examined cell lines. Our results suggest that encapsulating MS‐275 in TPGS micelles represents a promising strategy to enhance MS‐275 therapeutic impact while minimizing its pharmacological dosage.

Despite advancements in therapeutics, early diagnosis of ovarian cancer (OC) remains a challenge due to its asymptomatic progression and it is often diagnosed at an advanced stage. Interleukin-8 (IL-8), a pro-inflammatory chemokine with angiogenic activity, plays a pivotal role in inflammation and carcinogenesis. Therefore, it is of interest to investigate the association between IL-8 polymorphisms and OC risk. A novel non-synonymous SNP (nsSNP, c.193G>A; p.Glu65Leu) was identified in exon 2 of the IL-8 gene in 5 patients, 3 with stage III and 2 with stage II tumor. Structural analysis suggested that the p.Glu65Leu mutation alters the IL 8 protein conformation showing functional impairment. Thus, data shows that IL-8 c.193 G>A (Glu65Leu) polymorphism may contribute to tumor susceptibility. However, further studies are warranted to understand the role of IL-8 polymorphism in OC.