Triple-negative breast cancer (TNBC), characterized by its aggressive behavior and lack of targeted therapies, remains a major therapeutic challenge. This study presents the synthesis and evaluation of ferulic acid-loaded selenium nanoparticles (FA-SeNPs) coated with alginate (Alg@FA-SeNPs) and chitosan (CS@FA-SeNPs) as potential nanocarriers for TNBC treatment. Ferulic acid was selected for its pro-apoptotic and anti-metastatic properties, despite its limited bioavailability. Encapsulation in SeNPs enhanced its stability and delivery efficiency. Alg@FA-SeNPs exhibited greater cytotoxicity (IC50: 103.6 µg/mL) than CS@FA-SeNPs (IC50: 178 µg/mL) after 48 h. Gene expression analyses showed significant H2AX upregulation with Alg@FA-SeNPs, indicating genotoxic stress, and marked Bcl-2 downregulation with CS@FA-SeNPs, favoring apoptosis. Zeta potential measurements confirmed near-neutral surface charge for Alg@FA-SeNPs and strong positive charge for CS@FA-SeNPs, supporting good colloidal stability. These findings highlight the therapeutic promise of biopolymer-coated SeNPs, particularly alginate-coated formulations, as targeted drug delivery systems for TNBC.

Neuroblastoma is the most common extracranial childhood tumor and accounts for approximately 15% of pediatric cancer-related deaths. Further studies are needed to identify potential therapeutic targets for neuroblastoma. Monensin is an ionophore antibiotic obtained from Streptomyces cinnamonensis with known antibacterial and antiparasitic effects. No study has reported the effects of monensin on SH-SY5Y neuroblastoma cells by targeting the PI3K/AKT signaling pathway. The aim of this study was to investigate the antiproliferative effects of monensin alone and in combination with rapamycin in human SH-SY5Y neuroblastoma cells mediated by the PI3K/AKT signaling pathway. The effects of single and combination applications of monensin and rapamycin on SH-SY5Y cell proliferation were investigated by XTT, and their effects on the PI3K/AKT signaling pathway by RT-PCR, immunohistochemistry, immunofluorescence, and Western blotting. The combined effects of monensin and rapamycin on SH-SY5Y proliferation were most potent at 72 h (combination index < 1). The combination of monensin and rapamycin caused a significant decrease in the expression of P21RAS, AKT, and MAPK1 genes. Single and combined administrations of monensin and rapamycin caused a significant decrease in PI3K/AKT expression. Our results showed for the first time that monensin exerts an antiproliferative effect by targeting the PI3K/AKT signaling pathway in neuroblastoma cells. It is suggested that monensin and its combination with rapamycin may be an effective therapeutic candidate for treating neuroblastoma.

Background and Objectives: Neuroblastoma is the most common extracranial solid tumor in children, often presenting challenges in treatment due to its clinical and genetic heterogeneity. This study investigated the anticancer potential of Pelargonium sidoides root extract on the human neuroblastoma cell line (SH-SY5Y). Using XTT assays, ELISA-based oxidative stress markers, and RT-PCR analysis of apoptotic genes, the study explored the extract’s effects on cell proliferation, oxidative stress, and apoptosis. Materials and Methods: For the cell culture, SH-SY5Y human neuroblastoma cells were thawed, cultured, and maintained under appropriate conditions for experiments. The dose- and time-dependent activity of Pelorgonium sidoides extract on SH-SY5Y neuroblastoma cells was investigated by XTT assay. The change in the oxidative stress marker 8-Hydroxy-2′-deoxyguanosine (8-OhDG) level was determined by ELISA for the doses applied to the control group root extract at a concentration of 25 μg/mL. Total antioxidant status (TAS) and total oxidant status (TOS) were measured from the cells in the study group with the help of a commercial kit. The oxidative stress index (OSI) was calculated by dividing the TAS by the TOS and multiplying by 100. In order to evaluate the expression levels of apoptosis-related Bax, Bcl-2, Caspase-3, Caspase-8, and Caspase-9 genes at the mRNA level in control and dose group cells, RNA isolation was performed from the SH-SY5Y control and dose group cells (IC50 value). Results: It is observed that the P. sidoides substance inhibits proliferation in cells at 24 h (p < 0.05). As the dose increases, cell proliferation decreases (p < 0.05). The IC50 value was calculated to be 113.83 μg/mL at 24 h. The concentration of 8-OhDG increased in neuroblastoma cells as a result of P. sidoides extract treatment (p < 0.05). TOS levels increased in neuroblastoma cells treated with P. sidoides extract (p < 0.01). OSI levels increased in cells treated with P. sidoides extract (p < 0.001). BAX and Caspase-8 expression increased are statistically significant in the P. sidoides dose group (p < 0.05). Conclusions: P. sidoides extract induces apoptosis in neuroblastoma cells through oxidative stress and mitochondrial- and death receptor-mediated pathways. This study highlights the potential of P. sidoides as a complementary therapeutic agent for neuroblastoma, warranting further in vivo and clinical investigations to assess its safety and efficacy.

In the present research, metal–organic framework-5 (MOF-5) was synthesized and loaded with zerumbone (ZER@MOF-5), followed by the evaluation of its anticancer, antibacterial, antifungal, DNA-binding, and free radical scavenging potentials. The synthesized nanoparticles were characterized using X-ray diffraction, ultraviolet–visible spectroscopy, Fourier-transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, and scanning electron microscopy. The in vitro anticancer activity of ZER@MOF-5 was studied in a human breast cancer cell line (MCF-7) using the CCK-8 assay. The interaction of ZER@MOF-5 with pBR322 plasmid DNA was assessed by gel electrophoresis. The antimicrobial effect of ZER@MOF-5 was examined in gram-positive and gram-negative bacterial strains and yeast strains using the microdilution method. The free radical scavenging activity was assessed using the DPPH assay. Cytotoxicity assay revealed a notable enhancement in the anticancer activity of zerumbone upon its encapsulation into MOF-5. The IC₅₀ value for ZER@MOF-5 was found to be 57.33 µg/mL, which was lower than that of free zerumbone (IC₅₀: 89.58 µg/mL). The results of the DNA-binding experiment indicate that ZER@MOF-5 can bind to target DNA and cause a conformational change in DNA. The results of the antibacterial activity experiment showed that the antibacterial ability of ZER@MOF-5 was limited compared to free zerumbone. The results of the DPPH assay demonstrated that the antioxidant activity of free zerumbone was higher than that of ZER@MOF-5. MOFs encapsulate compounds within their porous crystalline structure, which leads to prolonged circulation time compared to single ligands. Although the unique structure of MOFs may limit their antibacterial and antioxidant activity in the short term, it may increase therapeutic efficacy in the long term. However, to fully understand the long-term antibacterial and antioxidant effects of the ZER@MOF-5, further comprehensive in vitro and in vivo experiments are necessary. This finding indicates that the MOF-5 could potentially be an impressive carrier for the oral administration of zerumbone.

Objectives: Transient Receptor Potential Ankyrin 1 (TRPA1) has emerged as a stress-responsive ion channel involved in calcium homeostasis, redox signaling, migration, and cancer cell survival; however, the therapeutic relevance of TRPA1 activation versus inhibition remains poorly understood. In this study, we comparatively investigated the anticancer potential of the TRPA1 agonist ASP7663 and the TRPA1 antagonist HC030031 across a broad panel of human cancer cell lines. Methods: Antiproliferative and cytotoxic effects were evaluated using MTT and LDH assays, while apoptotic signaling, DNA fragmentation, mitochondrial membrane potential, migration inhibition, DNA/BSA interactions, topoisomerase I inhibition, and molecular docking analyses were comprehensively assessed. Results: ASP7663 exhibited markedly lower GI₅₀ values than HC030031 in most cancer models and demonstrated favorable tumor selectivity relative to normal cells. Mechanistically, ASP7663 induced robust apoptotic activation characterized by significant upregulation of Caspase-3, Caspase-8, and Caspase-9, together with enhanced DNA fragmentation and pronounced nuclear condensation. Rhodamine-123 staining further revealed substantial mitochondrial membrane depolarization, indicating activation of intrinsic apoptotic pathways. In addition, ASP7663 produced selective membrane damage in malignant cells, stronger inhibition of migration in osteosarcoma and chondrosarcoma models, enhanced CT-DNA/BSA binding affinity, partial topoisomerase I inhibition, and superior docking interactions with apoptosis-related targets, including Caspase-3, Caspase-8, Caspase-9, Bax, and Bcl-2. Conclusions: Collectively, these findings suggest that ASP7663 is a promising multi-target candidate for anticancer therapy and support further investigation of TRPA1-associated pathways as potential therapeutic targets in cancer.