Background and Objectives: Oropharyngeal squamous cell carcinoma (OPSCC) is a common type of head and neck cancer with a progressive incidence in recent years. The limitations and the side effects associated with the current treatments require new therapeutic alternatives. Silibinin (SIL) is a phytocompound with multifaceted properties that has demonstrated antitumor effects in several types of cancer. The aim of this study was to assess the potential anticancer effects of SIL in Detroit 562 human pharyngeal cancer cells, an ideal model for HPV-negative OPSCC. Materials and Methods: Detroit 562 cells and HGF-1- human gingival fibroblasts were used as experimental models. For the mechanistic investigations, different methods, such as MTT assay, bright field microscopy, immunofluorescence staining, and specific assays and kits were applied to quantify intracellular ROS production, activation of caspases, and the colony formation assay. Results: Treatment with SIL (25–200 µM) for 48 h induced a selective cytotoxic effect in Detroit 562 cancer cells, being minimally toxic to healthy cells. The cytotoxic mechanism of action was characterized by a decreased cell viability, morphological alterations, elevation of intracellular ROS, decreased mitochondrial potential, mitochondrial and nuclear dysmorphologies, activation of caspases 9 and 3/7 and apoptosis occurrence, and decreased long-term colony formation. Conclusions: These findings show that SIL could represent a potential alternative therapy for HPV-negative OPSCC by triggering mitochondrial apoptosis and exerting a decline in the colonogenicity of Detroit 562 cancer cells.

Background: Aristolochia clematitis L. (AC), a plant with diverse traditional uses, has gained increasing scientific interest due to its rich content of bioactive compounds such as flavonoids and polyphenols. However, its systemic use is limited by the presence of aristolochic acids, which are known for their nephrotoxic and carcinogenic potential. Methods: In this context, the present study investigates the therapeutic potential of A. clematitis extract by encapsulating it in liposomes with the aim of enhancing its topical efficacy. Results: The extract was characterized in terms of its flavonoid content (67.23 ± 0.33 mg QE/g DW (quercetin/dry plant material)) and polyphenols expressed as gallic acid equivalents (64.38 ± 0.16 mg GAE/g DW), as well as its antioxidant capacity using the reagents 1,1-diphenyl-2-picrylhydrazyl (DPPH − IC₅₀ = 0.1619 mg/mL extract) and diammonium 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS − IC₅₀ = 205.57 μg/mL extract). Four types of liposomes were synthesized (two loaded with extract and two empty), and their characterization was performed using Atomic Force Microscopy (AFM), Dynamic Light Scattering (DLS), Zeta Potential, polydispersity index, and in vitro release studies. Conclusions: The results demonstrated a high entrapment efficiency (over 82%), good stability over 30 days, and controlled release of flavonoids. Microbiological studies revealed relevant antimicrobial activity against Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, and Pseudomonas aeruginosa strains. The evaluation on HaCaT skin-derived cells (at 10–100 µg/mL) proved that the samples displayed good overall tolerability, slightly decreasing cell viability (the most statistically significant being associated with AC treatment) and showing no structural, nuclear, or mitochondrial morphological changes.

Background/Objectives: Magnetic iron oxide nanoparticles are investigated in cancer research; however, the direct biological effects of unloaded magnetic colloidal suspensions in renal cancer remain insufficiently characterized. This study compared two double-oleic-acid-coated formulations prepared from precursors: magnetite-based MCS 1 and maghemite-based MCS 2. Methods: The suspensions were characterized by vibrating-sample magnetometry, dynamic light scattering, bright-field scanning transmission electron microscopy, and energy-dispersive X-ray spectroscopy. Their effects on A704 renal adenocarcinoma cells were evaluated after 24 h of exposure to 1–5 µg/mL using MTT, neutral red uptake, JC-1, Hoechst 33342/MitoTracker Red CMXRos, acridine orange/propidium iodide staining, and a 7-day clonogenic assay. Results: MCS 2 showed higher volumetric saturation magnetization (1.541 vs. 1.059 Gs), a smaller Z-average hydrodynamic diameter (79.65 vs. 103.9 nm), and a more uniform volume-weighted distribution. Both formulations significantly reduced metabolic activity and neutral red uptake and induced mitochondrial depolarization, cell-death-associated morphological changes, and impaired clonogenic capacity. MCS 1 generally produced a moderate response with an apparent plateau, whereas MCS 2 showed a pronounced concentration-related effect at 4–5 µg/mL. At 5 µg/mL, MCS 2 reduced metabolic activity to approximately 49%, neutral red uptake to 50.04%, the JC-1 aggregate-to-monomer ratio to 46.02%, and colony formation to 31.44% of the control. Conclusions: The suspensions exhibited distinct physicochemical and biological profiles. MCS 2 produced greater effects at the highest concentrations, potentially related to its smaller hydrodynamic size and more uniform particle-size distribution. Further studies should establish tumor selectivity, cellular uptake, and the underlying molecular mechanisms.

The skin serves as the first line of defense, being highly prone to external damage. Silibinin (SIL) exerts skin-protective properties, but its topical use requires a suitable delivery system. Despite the growing interest in proniosomal platforms loaded with natural products, their application for the cutaneous delivery of SIL remains scarcely explored. This study proposes the pharmaco-technical characterization and preclinical safety evaluation of a SIL-loaded proniosomal gel (SIL-PG) for skin application. SIL-PG was produced using the coacervation phase separation technique, analyzed in terms of physicochemical and technological properties, and evaluated in vitro and in ovo for potential cytotoxic and irritant effects. SIL-PG retained a yellowish, creamy aspect, proper rheological behavior and spreadability, gradual in vitro drug release, sustained permeation, and an adequate safety profile, evidenced by the lack of cytotoxicity in HaCaT keratinocytes and spheroids and the absence of irritant potential in 3D EpiDerm™ reconstructed human tissues and on the chorioallantoic membrane. Overall, these findings emphasize SIL-PG as a potential pharmaceutical formulation for dermal use, with favorable pharmaco-technical characteristics and in vitro–in ovo biocompatibility.

Background: Advanced malignant melanoma continues to be a highly invasive type of cancer with an unfavorable prognosis and limited therapeutic outcomes. Methods: The current study investigated the cytotoxic potential and morphological effects of genistein (GEN) and dexamethasone (DEX), administered individually and in combination, on murine melanoma cells B164A5, using normal epidermal cells JB6 Cl 41-5a as controls. Results: Treatment with GEN induced a dose-dependent decrease in the viability of melanoma cells, reaching 60.52% at 50 µM, in accordance with its known capacity to both inhibit proliferation and induce apoptosis by modulating NF-κB and Akt signaling pathways. DEX demonstrated moderate cytotoxic activity (71.34% viability at 50 µM), mirroring its recognized adjuvant role in cancer therapy. Combined treatment with both GEN (25 µM) and DEX (50 µM) resulted in the highest cytotoxicity (48.97% viability), suggesting a synergistic effect likely mediated by augmented apoptotic signaling and oxidative stress. The MTT assay and morphological analyses confirmed apoptotic characteristics, including cell contraction and detachment, while normal cells remained over 90% viable. Conclusions: These results show that GEN, especially when combined with DEX, has selective cytotoxicity against melanoma cells and may serve as a potentially promising adjuvant candidate for future pharmacological strategies targeting malignant melanoma.

Background/Objectives: Osteosarcoma (OS) is an aggressive cancer with high prevalence in children, adolescents and young adults. Catechin (CAT) presents broad-spectrum therapeutic potential, with previously studied anticancer properties. Metal complexation with zinc(II), Zn(II), and copper(II), Cu(II), emerged as a promising strategy for the development of improved metallodrugs against OS. The objective of this study was to comparatively evaluate the in vitro anticancer effect of CAT, catechin-zinc(II), CAT-Zn(II), and catechin-copper(II), CAT-Cu(II), in U2-OS cells used as 2D OS models. Methods: To achieve this, the impact of CAT and its metal complexes on the viability, morphology, proliferation, clonogenic capacity, migratory ability and apoptotic cell death in U2-OS cells was evaluated. Results: Our findings revealed that CAT-Cu(II) displays a comparable behavior to CAT, with low cytotoxicity, but strong anti-clonogenic and anti-migratory activities. In contrast, CAT-Zn(II) exerted prominent anti-tumor activity in vitro, with concentration-dependent reduction in cell viability (from 88.34% at 0.1 mM, to 5.50% at 0.5 mM) and proliferation inhibition, strong suppression of colony formation and migration rates (below 10% and 50%, respectively), marked alterations in mitochondrial membrane potential and apoptosis-associated changes. These biological effects were correlated with KI67, metalloproteinase-2 (MMP-2) and vimentin downregulation, and BAX upregulation. Conclusions: The investigated catechin–metal preparations showed distinct biological effects in U2-OS cells. CAT-Zn(II) caused the greatest reductions in cell viability and proliferation, along with mitochondrial alterations and apoptosis-associated changes. CAT-Cu(II), by contrast, had limited cytotoxicity but reduced colony formation and wound closure. These findings support further study of CAT-Zn(II) in additional experimental models.