OBJECTIVE: Irinotecan-based combination chemotherapies in malignant gliomas need to be examined. The aim of this study was to investigate the synergetic effect of ellagic acid, a natural polyphenolic antioxidant compound, with irinotecan, an inhibitor of topoisomerase I enzyme, on the growth, cadherin switch, and angiogenic processes of a glioma cell line. METHODS: A combination of 100 mu M ellagic acid and 100 mu M irinotecan was applied to rat C6 glioma cells for 24th, 48th, and 72nd h. The cell proliferation was evaluated by 5-bromo-2'-deoxyuridine immunocytochemistry. The expression levels of vascular endothelial growth factor, E-cadherin, and N-cadherin were measured using real-time polymerase chain reaction and their immunoreactivities using immunocytochemistry. RESULTS: The treatment of irinotecan with combining ellagic acid enhanced antitumor activity and the synergistic effect of these reduced the cell proliferation of C6 glioma by inhibiting the cadherin switch and promoting the antiangiogenic processes. CONCLUSIONS: Further research is required to prove a negative relationship between C6 glial cell proliferation and irinotecan with ellagic acid application. Our preliminary data suggest that even with the extremely short-term application, irinotecan with ellagic acid may affect glioma cells at the level of gene and protein expression.

Purpose To investigate the efficacy of cordycepin, an adenosine analogue, on prevention of esophageal damage and stricture formation due to esophageal caustic burns in rat model comparing with prednisolone. Methods Caustic esophageal burn was introduced by 37.5% of NaOH to distal esophagus. Thirty-two Wistar albino rats were divided in four groups: sham rats undergone laparotomy, treated with 0.9% NaCl; control rats injured with NaOH without cordycepin treatment; cordycepin group injured with NaOH, treated with 20 mg/kg cordycepin; prednisolone group injured with NaOH, treated with 1 mg/kg prednisolone for 28 days. Efficacy was assessed by histopathological and immunohistochemical analysis of esophageal tissues. Results Cordycepin treatment significantly decreased inflammation, granulation tissue and fibrous tissue formation and prevented formation of esophageal strictures shown by histopathological damage score and stenosis indexes compared to control group (p < 0.01). These effects are relatively more substantial than prednisolone, probably based on attenuation of elevation of proinflammatory cytokines hypoxia-inducible factor 1-alpha (HIF-1?), tumor necrosis factor alpha (TNF-?), proliferative and fibrotic factor fibroblast growth factor 2 (FGF2) and angiogenic factor vascular endothelial growth factor A (VEGFA) (p < 0.05). Conclusions The findings suggest that cordycepin has a complex multifactorial healing process in alkali-burned tissue, more successful than prednisolone in preventing the formation of esophageal strictures and may be used as a therapeutic agent in the acute phase of esophageal alkali-burn.

Background: Ovarian cancer (OC) is characterized by aggressive progression, high metastatic potential, and frequent resistance to conventional chemotherapy, highlighting the need for novel combination-based therapeutic strategies. Metformin has emerged as a promising antineoplastic agent; however, its efficacy may be enhanced through combination with bioactive compounds. This study aimed to investigate the antineoplastic effects of metformin in SKOV3 human OC cells and to evaluate whether these effects could be potentiated by boric acid (BA) and resveratrol, with particular emphasis on their modulatory impact on key inflammatory and tumor-associated biomarkers, including interleukin-17 (IL-17), nuclear factor kappa-B (NF-κB), and midkine (MDK). Methods: SKOV3 cells were treated with metformin, BA, and resveratrol as monotherapies or in combination. Cell viability was assessed using a colorimetric assay, while migratory capacity was evaluated by wound healing analysis. The expression levels of IL-17, NF-κB, and MDK were quantified in cell lysates, and p21 protein expression was analyzed by immunocytochemistry. Results: All treatments induced concentration- and time-dependent reductions in cell viability. Combination treatments, particularly metformin with boric acid or resveratrol, produced more pronounced inhibitory effects on cell survival and migration compared with single-agent treatments. Inflammatory and tumor-associated biomarkers, including IL-17, NF-κB, and MDK, were significantly modulated following treatment. Additionally, increased p21 expression was observed in treated cells, indicating enhanced cell cycle regulatory activity. Conclusions: These findings indicate that BA and resveratrol enhance the antineoplastic activity of metformin in SKOV3 OC cells by suppressing proliferative and migratory capacities and modulating inflammatory mediators such as IL-17, NF-κB, and MDK. However, since toxicity assessments in non-cancerous cells were not performed, the safety profile of this combination remains unclear and requires further investigation in non-cancerous models.

Background/Objectives: Endometrial cancer frequently develops resistance to thera-py, partly due to the ability of tumor cells to adapt to cellular stress through non-apoptotic mechanisms. Mitochondrial dysfunction and cytoskeletal remodeling are increasingly recognized as key components of stress adaptation; however, their structural relationship under pharmacological stress in three-dimensional (3D) tumor models remains poorly characterized. The present study aimed to investigate the ul-trastructural and phenotypic effects of lithium chloride (LiCl)–induced stress in 3D endometrial cancer spheroids, with a particular focus on mitochondrial alterations and intermediate filament organization. Methods: Three-dimensional spheroids gen-erated from Ishikawa endometrial cancer cells were exposed to lithium chloride at concentrations of 1, 10, or 50 mM for defined time periods. Cell viability, proliferative activity, and clonogenic capacity were assessed using Trypan Blue exclusion, BrdU in-corporation, and soft agar assays. Ultrastructural changes were examined by trans-mission electron microscopy to evaluate mitochondrial morphology, cytoplasmic or-ganization, and intermediate filament distribution. Results: LiCl exposure resulted in a dose- and time-dependent reduction in cell viability, proliferation, and clonogenic potential in 3D spheroids. Ultrastructural analysis revealed pronounced mitochondrial swelling, cristae disorganization, and membrane-associated mitochondrial alterations. These changes were consistently accompanied by conspicuous accumulation and re-organization of intermediate filaments in close spatial proximity to damaged mito-chondria. Across all experimental conditions, classical apoptotic ultrastructural fea-tures, including chromatin condensation and apoptotic body formation, were not ob-served, despite substantial organelle-level alterations. Conclusions: Together, these observations indicate that lithium chloride elicits a stress phenotype in 3D endometrial cancer spheroids that primarily manifests at the organelle and cytoskeletal levels, ra-ther than through classical apoptotic execution. Although descriptive in nature, the present study highlights intermediate filament accumulation as a prominent structural feature of lithium-induced mitochondrial stress and establishes a structural reference point for future studies aimed at dissecting mitochondrial–cytoskeletal interplay dur-ing pharmacological stress in endometrial cancer.

Background/Objectives: Endometrial cancer frequently develops resistance to therapy, partly due to the ability of tumor cells to adapt to cellular stress through non-apoptotic mechanisms. Mitochondrial dysfunction and cytoskeletal remodeling are increasingly recognized as key components of stress adaptation; however, their structural relationship under pharmacological stress in three-dimensional (3D) tumor models remains poorly characterized. The present study aimed to investigate the ultrastructural and phenotypic effects of lithium chloride (LiCl)-induced stress in 3D endometrial cancer spheroids, with a particular focus on mitochondrial alterations and intermediate filament organization. Methods: Three-dimensional spheroids generated from Ishikawa endometrial cancer cells were exposed to lithium chloride at concentrations of 1, 10, or 50 mM for defined time periods. Cell viability, proliferative activity, and clonogenic capacity were assessed using Trypan Blue exclusion, BrdU incorporation, and soft agar assays. Ultrastructural changes were examined by transmission electron microscopy to evaluate mitochondrial morphology, cytoplasmic organization, and intermediate filament distribution. Results: LiCl exposure resulted in a dose- and time-dependent reduction in cell viability, proliferation, and clonogenic potential in 3D spheroids. Ultrastructural analysis revealed pronounced mitochondrial swelling, cristae disorganization, and membrane-associated mitochondrial alterations. These changes were consistently accompanied by conspicuous accumulation and reorganization of intermediate filaments in close spatial proximity to damaged mitochondria, suggesting a structural association between cytoskeletal remodeling and mitochondrial injury. Across all experimental conditions, classical apoptotic ultrastructural features, including chromatin condensation and apoptotic body formation, were not observed. Conclusions: Together, these observations indicate that lithium chloride elicits a stress phenotype in 3D endometrial cancer spheroids that primarily manifests at the organelle and cytoskeletal levels, rather than through classical apoptotic execution. Although descriptive in nature, the present study highlights intermediate filament accumulation as a prominent structural feature of lithium-induced mitochondrial stress and establishes a structural reference point for future studies aimed at further investigating mitochondrial–cytoskeletal relationships during pharmacological stress in endometrial cancer.

Breast cancer (BC) remains the most diagnosed malignancy among women worldwide, with approximately 2.3 million new cases and over 670,000 deaths reported annually. Resistance to conventional chemotherapeutic agents and treatment-related toxicity remain major challenges in BC management. Resveratrol, a naturally occurring polyphenol, has been proposed as a potential modulator of chemotherapy response; however, comparative evidence regarding its interaction with different classes of chemotherapeutic agents is limited. This study aimed to comparatively assess the effects of resveratrol on the cytotoxic, antiproliferative, and apoptotic responses induced by adriamycin, taxol, and cisplatin in MCF-7 BC cells. MCF-7 cells were treated with adriamycin, taxol, cisplatin, and resveratrol, either alone or in combination, across multiple concentrations for 24, 48, 72, and 96 h. Cell viability was evaluated using the trypan blue exclusion assay. Cellular proliferation was assessed via BrdU incorporation, while apoptosis and cell death profiles were analyzed using Annexin V staining and flow cytometry. Exposure to individual chemotherapeutic agents induced a significant time- and dose-dependent reduction in MCF-7 cell viability (p < 0.001). Resveratrol co-treatment further modulated chemotherapy-induced cytotoxicity in an agent- and time-dependent manner. Combination treatments markedly suppressed DNA synthesis compared with single-agent exposure (p < 0.01) and significantly increased apoptotic cell populations. Flow cytometric Annexin V/PI analysis demonstrated that early apoptotic cells ranged from 3.2–11.3% in single-agent treatments and increased to 0.04–50.4% in resveratrol-based combination groups. Similarly, late apoptotic/secondary necrotic cell fractions increased from 4.1–4.4% in single-agent treatments to 2.1–69.9% following combination therapy, indicating a substantially higher overall cell death response in selected treatment conditions. This study demonstrates that resveratrol modulates the cytotoxic and apoptotic responses of MCF-7 BC cells to adriamycin, taxol, and cisplatin in an agent- and time-dependent manner. The findings indicate that resveratrol acts as a context-dependent modulator of chemotherapy response. Although resveratrol generally enhanced cytotoxic and apoptotic responses in combination treatments, the magnitude of these effects varied depending on the chemotherapeutic agent and exposure conditions. Further preclinical and clinical studies are warranted to define their therapeutic relevance.