Search Results (1,233)

Background: Chronic myeloid leukemia (CML) and other leukemia subtypes remain significant hematological malignancies that require the development of novel therapeutic agents with improved efficacy and selectivity. This study aimed to design, synthesize, and evaluate novel oleanolic acid (OA) derivatives as potential anti-leukemic agents. Methods: Structural modifications at the C-28 position afforded halogenated benzyl ester derivatives (MT-A–D), while aromatic acyl substitutions at the C-3 position generated derivatives NOA-1–16. The cytotoxic effects of the synthesized compounds were evaluated against K562, HL-60, Jurkat, and MT-2 leukemia cell lines and healthy PBMCs using the MTT assay. Apoptosis induction and ABL tyrosine kinase (TK) inhibition were also investigated. Molecular docking, MM/GBSA binding free energy calculations, and molecular dynamics (MD) simulations were performed to characterize ligand-enzyme interactions and binding stability. Results: MT-A exhibited the highest activity against HL-60 cells (IC₅₀ = 4.17 ± 0.65 μM), surpassing imatinib (IC₅₀ = 13.34 ± 1.92 μM). NOA-8 was the most potent compound against Jurkat and MT-2 cells, with IC₅₀ values of 6.81 ± 1.08 μM and 2.48 ± 0.88 μM, respectively. MT-A, MT-C, NOA-3, and NOA-8 displayed IC₅₀ values above 300 μM in PBMCs, indicating favorable selectivity. MT-A and MT-C induced significant apoptosis in K562 cells, while kinase assays revealed moderate ABL TK inhibition by these compounds. Docking, MM/GBSA, and MD analyses supported stable binding of MT-A and MT-C within the ABL ATP-binding pocket. Conclusions: MT-A, MT-C, NOA-3, and particularly NOA-8 emerged as promising anti-leukemic lead compounds with potent antiproliferative activity and favorable selectivity profiles, warranting further investigation for leukemia therapy. Full article

Background/Objectives: This study engineered and evaluated a targeted, folate-functionalized chitosan nanoparticle (CS-FA NP) delivery system to enhance the therapeutic efficacy of standard quercetin and Coriandrum sativum seed extract against breast cancer. Methods: Phytochemical profiling confirmed a 14% crude yield for the methanolic extract, with gas chromatography–mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) identifying quercetin as the principal bioactive agent. The synthesized CS-FA NPs exhibited a core size of 7–20 nm, an average hydrodynamic diameter of 150–160 nm, a stable zeta potential of −55 mV, and high encapsulation efficiencies (87.2% for quercetin and 80.5% for coriander). Kinetic assessments confirmed a biphasic, diffusion-controlled release matching Higuchi matrix kinetics. Anticancer activity was evaluated in vitro using MTT cytotoxicity, Annexin V-FITC/PI apoptosis analysis, RT-qPCR, and ex vivo rat aortic ring assays, followed by validation in a syngeneic 4T1 mammary tumor mouse model. Results: In vitro, folate-receptor-targeted quercetin nanoparticles (T4) demonstrated superior, selective cytotoxicity, particularly against triple-negative MDA-MB-231 cells, while sparing normal fibroblasts. Annexin V-FITC/PI apoptosis profiling and ex vivo aortic ring assays revealed profound, cell-line-dependent programmed cell death and up to 90% inhibition of microvessel sprout outgrowth. Mechanistically, RT-qPCR verified that nano-formulations induced complete transcriptional silencing of NANOG, MMP-1, VEGFA, TSPAN8, TWIST, EMMPRIN, and CDK1, alongside marked upregulation of P27^KIP1 and P21^CIP1. In vivo, these nano-formulations successfully improved tumor-associated pathological features, reduced aggressive tumor spindle-cell proliferation, and suppressed elevated serum CA15-3 and arginase biomarkers. Conclusions: Folate-functionalized chitosan nano-formulations significantly enhanced the anticancer efficacy of quercetin and Coriandrum sativum seed extract through improved targeted delivery, potent antiproliferative, anti-angiogenic, and pro-apoptotic activities, together with favorable modulation of multiple molecular pathways associated with breast cancer progression. These findings support their potential as promising targeted nanotherapeutic strategies for breast cancer treatment. Full article

Imidazolium salt derivatives (IMSDs) represent a structurally diverse class of compounds that has attracted increasing interest as a source of novel anticancer agents due to their tunable chemical architecture and broad spectrum of biological activities. This review summarizes current advances in the development of organic imidazolium derivatives and metal–N-heterocyclic carbene (NHC) complexes, with particular emphasis on their structure–activity relationships (SARs), mechanisms of action, and therapeutic potential. Numerous IMSDs exhibit significant antiproliferative activity against a wide range of cancer cell lines through multiple mechanisms, including DNA damage, reactive oxygen species generation, mitochondrial dysfunction, thioredoxin reductase inhibition, cell-cycle arrest, and apoptosis induction. Among the reported compounds, Au(I)-, Pt(II)-, and Ag(I)-NHC complexes consistently demonstrate the highest cytotoxic potency, whereas hybrid derivatives incorporating pharmacologically active moieties, such as lithocholic acid, have been investigated as potential approaches to improving selectivity and multitarget activity. Current SAR analyses indicate that metal coordination, bulky aromatic substituents, molecular hybridization, and balanced lipophilicity are key determinants of enhanced biological activity. Despite these encouraging findings, most available evidence is limited to in vitro studies, while comprehensive in vivo evaluation, pharmacokinetic characterization, and systematic toxicological assessment remain insufficient. Consequently, the clinical relevance of these compounds has yet to be established. Future research should focus on rational structural optimization, standardized preclinical evaluation, combination therapies, and advanced drug delivery strategies, including nanomedicine, to facilitate the translation of IMSDs into clinically useful anticancer agents. Full article

Background and Objectives: Melissa officinalis (lemon balm) contains phenolic constituents with antioxidant and cytotoxic activities; however, evidence regarding aqueous leaf extracts in lung adenocarcinoma models and reconstructed human airway tissues remains limited. The novelty of the present study lies in the integrated evaluation of the same aqueous extract through phytochemical and antioxidant characterization, a three-dimensional reconstructed tracheobronchial tissue model, and complementary short- and long-term biological endpoints in A549 lung adenocarcinoma cells. Materials and Methods: Antioxidant activity was evaluated using the DPPH assay, total phenolic content (TPC) using the Folin–Ciocalteu method, and the targeted phenolic profile using UHPLC–MS/MS. EpiAirway^TM tissues were exposed to 1000 µg/mL extract for 24 h, and tissue metabolic viability was assessed using the MTT assay. A549 cells were treated with 20–1000 µg/mL extract for 24 h and evaluated using complementary metabolic, lysosomal, mitochondrial, morphological, membrane-integrity, and clonogenic endpoints. Results: The extract exhibited concentration-dependent DPPH radical-scavenging activity, with an estimated IC₅₀ of 1.37 mg/mL (95% CI: 1.00–1.88 mg/mL), and a TPC of 10.84 ± 0.03 mg GAE/g dry extract. The most abundant targeted analytes were the unresolved 3,5-dihydroxybenzoic acid/3,4-dihydroxybenzoic acid group (2.09 ± 0.60 µg/mL) and the p-coumaric acid/trans-p-coumaric acid group (1.31 ± 0.04 µg/mL). EpiAirway^TM tissue viability was 85.87% following exposure to 1000 µg/mL. In A549 cells, metabolic viability decreased to approximately 59% and 53% at 500 and 1000 µg/mL, respectively, whereas neutral red uptake declined to approximately 50% at 1000 µg/mL. Treatment was also associated with mitochondrial membrane depolarization, concentration-dependent cellular and nuclear alterations, apoptotic-like and necrotic staining patterns, and a reduction in clonogenic capacity to approximately 21% at 1000 µg/mL. Conclusions: The aqueous M. officinalis leaf extract exhibited measurable antioxidant activity, did not cause a marked acute reduction in EpiAirway^TM tissue metabolic viability under the single exposure condition tested, and produced concentration-dependent cytotoxic and sustained antiproliferative effects in A549 cells. These exploratory findings do not establish comprehensive respiratory safety, a specific cell-death mechanism, or tumor selectivity. Nevertheless, the integrated experimental approach supports further investigation using standardized multiple extract batches, matched malignant and non-malignant lung epithelial models, and quantitative molecular endpoints. Full article

Histamine is a biologically active monoamine acting through four G protein-coupled receptors (H₁R–H₄R), which represent attractive therapeutic targets for a range of diseases. Nowadays, H₄R is recognized as a key player in inflammation and cancer. Here, we describe the design, syntheses and characterization of new H₄R ligands containing pyrido[2,3-d]pyrimidine or pyrimidine scaffold. Candidate structures were scored in silico by docking to the structure of the human inactive H₄R. Favorable structures were synthesized and, after confirmation of identity, their affinities were verified in in vitro screenings. Tested compounds did not exhibit any relevant cytotoxic (PrestoBlue) or antiproliferative (BrdU incorporation) effects at concentrations used in the functional assays. In a radioligand displacement assay (H₄R affinity) the pyrimidine series showed lower binding, whereas several pyrido[2,3-d]pyrimidine derivatives and one pyrimidine analog produced >60% inhibition at 1 µM. Two similar compounds with the highest and moderate affinities were selected for further studies. In the G_i–cAMP pathway, both compounds behaved as moderate H₄R antagonists, but in contrast, their profiles diverged in the β-arrestin pathway. These findings suggest ligand-dependent biased differences in signaling across G-protein and β-arrestin pathways at H₄R. Overall, YAN-153 emerges as a promising lead structure for further optimization and for more detailed in vitro (e.g., metabolic stability, selectivity) and in vivo studies. Full article

Background/Objectives: Isorhamnetin is a naturally occurring flavonoid with reported antioxidant, anti-inflammatory, and anticancer properties. Although its biological activities have been extensively investigated, its effects on ovarian cell physiology remain insufficiently characterized. This study aimed to evaluate the influence of isorhamnetin on the viability, steroid hormone secretion, apoptosis, and growth factor signalling in human ovarian cell lines representing both non-tumour and tumour phenotypes. Methods: Human granulosa (HGL5), granulosa tumour (COV434), and epithelial ovarian carcinoma (OVCAR-3) cell lines were treated with isorhamnetin at concentrations of 5–80 μg/mL for 24 h. Cell viability was determined using the AlamarBlue^TM assay. The secretion of progesterone, 17β-estradiol, and the presence of transforming growth factor β2 (TGF-β2), transforming growth factor β receptor 2 (TGFBR2), and apoptosis-inducing factor (AIF) was quantified by enzyme-linked immunosorbent assay (ELISA). Results: Isorhamnetin significantly reduced cell viability in a dose-dependent manner, with tumour cell lines exhibiting greater sensitivity than non-tumour granulosa cells. A significant decrease in viability was observed in OVCAR-3 cells from 10 μg/mL onward, whereas COV434 cells showed significant reductions at concentrations of 20 μg/mL and higher. In contrast, HGL5 cell viability was significantly affected only at the highest concentration (80 μg/mL). No significant changes were detected in the secretion of progesterone, 17β-estradiol, TGF-β2, or TGFBR2 in any of the examined cell lines. A significant reduction in AIF production was observed only in HGL5 cells treated with 80 μg/mL isorhamnetin. Conclusions: Isorhamnetin preferentially decreased the viability of ovarian tumour cells while exerting only limited effects on non-tumour granulosa cells, indicating preferential cytotoxic activity toward malignant ovarian cells. The absence of significant changes in steroid hormone production and TGF-β suggests that its antiproliferative effects involve molecular pathways that were not investigated in the present study. These findings support further investigation of isorhamnetin as a potential natural compound for ovarian cancer prevention or adjunctive therapy. Full article

Rosmarinic acid (RA), a naturally occurring polyphenolic compound, has attracted increasing attention because of its potential anticancer activity and capacity to modulate oxidative stress-associated signaling pathways. In the present study, the cytotoxic, apoptotic, and antiproliferative effects of RA, alone or in combination with gemcitabine (Gem), were investigated in OVCAR3 ovarian cancer cells and HaCaT keratinocytes using integrated two-dimensional and three-dimensional (3D) experimental models. Cell viability assays demonstrated dose- and time-dependent growth inhibition following RA and Gem treatment, while combination index (CI) analysis revealed synergistic cytotoxic activity in OVCAR3 cells. Flow cytometric analyses showed that combined treatment markedly increased apoptotic cell populations and altered cell cycle progression through enhanced S-phase and G2/M accumulation. Intracellular reactive oxygen species (ROS) levels were significantly elevated following combination treatment, and N-acetyl-L-cysteine (NAC) pretreatment partially attenuated both ROS accumulation and cytotoxicity, indicating a functional contribution of oxidative stress to the observed antitumor response. RT-qPCR analyses demonstrated increased expression of proapoptotic genes (BAX, CASP3, and CASP9) together with suppression of BCL2, MKI67, and CDK4 expression, while immunocytochemical analyses supported enhanced caspase-3 activation at the protein level. In 3D OVCAR3 tumor spheroids, the RA + Gem combination significantly reduced spheroid viability, disrupted spheroid architecture, and increased dead-cell accumulation compared with single-agent treatments. Collectively, these findings suggest that RA may enhance the anticancer activity of Gem in ovarian cancer cells through mechanisms associated with oxidative stress, apoptosis, and proliferation-related signaling pathways under both monolayer and 3D culture conditions. Full article

Exopolysaccharides (EPS) from microalgae have emerged as promising natural anticancer agents owing to their selective cytotoxicity toward tumor cells and low toxicity to healthy tissues. However, the molecular mechanisms and targets underlying their anticancer activity remain poorly understood. In the present study, EPS isolated from Coelastrella sp. BGV was evaluated for cytotoxicity and antiproliferative activity against a panel of human cancer cell lines (HepG2, HCT116, A549, and MDA-MB-231). The effects of EPS on mitochondrial function, cell cycle progression, apoptosis, and autophagy were investigated using flow cytometry and fluorescence microscopy. To gain mechanistic insight, molecular docking of a representative EPS disaccharide, α-L-Fucp-(1→6)-β-D-Galp, was performed against DC-SIGN and galectin-3 using the CB-Dock2 platform with the AutoDock Vina engine. The EPS exhibited minimal cytotoxicity toward non-tumor cells, and induced significant concentration-dependent antiproliferative activity in all tested cancer cell lines. MDA-MB-231 breast cancer cells were the most sensitive, with an IC₅₀ value of 57.5 ± 10 µg/mL and a selectivity index of 5.2 relative to non-tumor cells. Mechanistically, EPS treatment induced mitochondrial membrane depolarization, S-phase cell cycle arrest, autophagy, and apoptosis, as demonstrated by nuclear fragmentation, chromatin condensation, and increased Annexin V positivity. Molecular docking identified DC-SIGN and galectin-3 as plausible molecular targets, suggesting potential anticancer activity of Coelastrella sp. BGV EPS that may involve both direct pro-apoptotic effects and modulation of carbohydrate-mediated signaling pathways. Collectively, these findings provide new mechanistic insight into the anticancer activity of Coelastrella sp. BGV EPS and support its further investigation as a promising natural candidate for adjunctive cancer therapy. Full article

Colorectal cancer (CRC) treatment with standard chemotherapeutics such as capecitabine (CAP) and irinotecan (IRT) is frequently limited by toxicity and resistance. To identify novel adjuvant strategies, we investigated the dichloromethane–methanol (DM) Soxhlet extract of the red alga Jania rubens, previously shown to exert intrinsic antiproliferative effects via reactive oxygen species (ROS) induction, inhibition of epithelial–mesenchymal transition (EMT), and suppression of TET enzymes. The present study evaluated the effect of the DM extract in combination with chemotherapeutic agents in HCT-116, Caco-2, and HT-29 colorectal cancer cell lines, assessing its potential to enhance treatment response. Co-treatment with the DM extract significantly enhanced the cytotoxic and anti-migratory effects of CAP and IRT in HCT-116 and Caco-2 cells. Combination treatment also impaired long-term clonogenic survival, suggesting the inhibition of therapy-resistant subpopulations. Flow cytometric analysis (Annexin V-FITC/PI) revealed a dose-dependent increase in apoptosis in HCT-116 cells following DM treatment. Western blot analysis further supported the pro-apoptotic activity of the DM extract by demonstrating reduced BCL-2 protein expression. The extract additionally modulated the mRNA expression levels of cytokines (TNF-α, IL-6, and IL-10), suggesting potential immunomodulatory effects in colorectal cancer cells. Notably, co-administration of IRT and the DM extract enhanced apoptosis, primarily through the downregulation of the anti-apoptotic gene BCL-2. Together, these findings indicate that the Jania rubens DM extract modulates multiple cellular pathways and enhances the response to conventional CRC chemotherapeutic agents. Full article

Bacterioruberin (BR), a C₅₀ carotenoid produced by halophilic archaea, is emerging as a bioactive molecule with potential anticancer relevance, but its activity in solid tumour and multidrug-resistant (MDR) models remains poorly defined. This in vitro study evaluated the cytotoxic, antiproliferative and growth-inhibitory effects of a chemically characterized bacterioruberin-rich carotenoid extract (BRCE) from Haloferax (H.) mediterranei in A549 lung adenocarcinoma, BT-549 triple-negative breast cancer and WM115 melanoma cells, as well as in paired sensitive/multidrug resistant (MDR) lung cancer models. Metabolic activity and proliferation were assessed by thiazolyl blue tetrazolium bromide (MTT) and carboxyfluorescein diacetate succinimidyl ester (CFDA-SE) assays, intracellular reactive oxygen species (ROS) by 2′,7′-dichlorodihydrofluorescein diacetate (H₂DCFDA) staining, and apoptosis-associated morphology by acridine orange/ethidium bromide (AO/EB) staining. Growth inhibition in A549/A549-CDR2 and NCI-H460/NCI-H460/R cells was analysed by sulforhodamine B (SRB) assay, while P-glycoprotein (P-gp) function and expression were examined using Rhodamine 123 (Rh123) accumulation and Western blotting. BRCE reduced metabolic activity and proliferation in a concentration- and time-dependent manner, increased intracellular ROS levels, and induced apoptosis-associated morphological changes in A549 cells. In MDR models, BRCE retained comparable growth-inhibitory activity in sensitive and resistant cells and partially attenuated P-gp-related drug efflux. These findings support further mechanistic investigation of BR in solid tumour and MDR cancer models. Full article

Background: Pituranthos scoparius (Apiaceae), commonly known in Algeria as “Kozah”, is a medicinal plant traditionally used for various therapeutic purposes. However, its potential as a source of antiproliferative agents and its underlying molecular mechanisms remain poorly characterized. Purpose: This study aimed to investigate the antiproliferative potential of P. scoparius through an integrated strategy combining phytochemical profiling, in vitro evaluation, and computational approaches, with particular emphasis on its activity against key cancer-related pathways. Study Design: An integrated experimental–computational study was performed to explore the multitarget antiproliferative profile of P. scoparius extracts. Methods: Phytochemical characterization was carried out using LC-MS/MS and GC-MS/MS to identify the major bioactive constituents. Antiproliferative activity was assessed in vitro against human colorectal (HT-29) and hepatocellular carcinoma (HepG2) cell lines using the MTT assay. Molecular docking studies were conducted on selected major metabolites against relevant oncogenic targets, including PI3Kα, mTOR, COX-2, and BCL-2, to investigate potential mechanisms of action. Machine learning approaches were further employed to support the prediction of multitarget antiproliferative activity. Results: Chlorogenic acid and trans-ferulic acid were identified as the predominant phenolic compounds, while α-pinene was the major constituent of the essential oil. Both preparations exhibited significant dose- and time-dependent antiproliferative effects, with the essential oil showing enhanced cytotoxicity (IC₅₀ up to 35.4 µg/mL). In silico analyses revealed strong binding affinities of key metabolites toward critical oncogenic proteins, particularly within the PI3Kα/mTOR signaling pathway. Machine learning predictions further supported a multitarget antiproliferative profile. Conclusions: P. scoparius represents a promising source of natural compounds with multitarget antiproliferative potential. The combined experimental and computational findings provide mechanistic insights into its activity and support its relevance within the context of natural product-based cancer therapy, highlighting its potential for further preclinical development. Full article

Selenium biofortification of edible sprouts is a promising strategy to enhance the cancer cell growth-inhibitory potential of plant-based foods. This study investigated the effects of selenium (Se)-enriched sunflower sprout extracts on human colorectal adenocarcinoma HT-29 cells in comparison with non-enriched sprouts. Cytotoxicity was evaluated by MTT assay, clonogenic survival by colony formation assay, wound closure by wound-healing assay, apoptosis- and cell cycle-related gene expression by qRT-PCR, and protein expression by Western blotting. Metabolite profiles were characterized using LC-MS/MS-based untargeted metabolomics. Se enrichment markedly enhanced cytotoxicity, reducing the IC₅₀ from 413.80 ± 6.00 (control) to 152.90 ± 6.00 µg/mL and increasing Emax from 59.29 ± 0.11% (control) to 75.70 ± 0.49%. The Se-enriched extract showed greater inhibition of colony formation (IC₅₀ 53.72 ± 1.12 µg/mL) and wound closure (IC₅₀ 76.07 ± 0.06 µg/mL). At the molecular level, Se-enriched sprouts upregulated Bax, caspase-3 and p21, downregulated Bcl-2, CDK4, NF-κB p65 and MMP-9, and increased Bax and p21 protein levels, linked with apoptosis-related signaling and cell cycle modulation. Metabolomics revealed significant increases in purine-related metabolites, lysophosphatidylcholine (LPC) 18:3, and choline, alongside decreases in several quinic acid derivatives and related phenolic metabolites. Se enrichment enhanced the in vitro antiproliferative activity of sunflower sprout extract in HT-29 cells and may modulate apoptosis- and cell cycle-related markers. These findings support further mechanistic and in vivo investigations of Se-enriched sunflower sprouts as a candidate functional food ingredient. Full article

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. Full article

Medicinal plants are a rich source of biologically active compounds, including phenolic acids, flavonoids, ellagitannins and other secondary metabolites. However, the contribution of specific groups of phenolic compounds to antiproliferative activity remains insufficiently clarified. This study extends our previous crude-extract screening by evaluating whether C18 solid-phase extraction (SPE) fractions with different phenolic profiles are associated with different antiproliferative responses. In parallel, extraction strategies were compared to assess method-dependent changes in phenolic recovery and antioxidant capacity, and an additional single-species vegetation-stage analysis of Chamaenerion angustifolium L. Holub was performed to evaluate harvest-stage effects. Phytochemical characterisation was performed using spectrophotometric assays and high-performance liquid chromatography (HPLC) analyses. Among the tested extraction methods, 75% (v/v) methanol in water was the most effective conventional solvent, and ultrasound-assisted extraction yielded the highest overall TPC (total phenolic content), TFC (total flavonoid content), and RSA (radical scavenging activity) values. Vegetation stage analysis of C. angustifolium L. Holub revealed significant variation in phenolic content and antioxidant activity, with the highest levels observed at the beginning of the flowering. Antiproliferative activity was assessed against five cancer cell lines (4T1, A549, Caki-1, HCT116 and MCF7), while HEK-293 cells were used as an immortalised non-cancerous reference model for general cytotoxicity evaluation. Linear mixed-model analysis confirmed a significant incubation-time effect in all tested cancer cell lines, with IC₅₀ values generally decreasing after prolonged exposure. Statistically significant F2-F3 differences were plant-dependent. The 30% (v/v) methanol in water fraction (F2), enriched in oenothein B in C. angustifolium L., showed stronger antiproliferative activity, whereas the 60% (v/v) methanol in water fraction (F3) showed stronger activity in Quercus robur L., Juglans nigra L., Juglans regia L., and Solidago canadensis L. These findings indicate that antiproliferative activity was associated with the qualitative and quantitative composition of the selected phenolic-rich SPE fractions rather than with a single universal fraction effect. All tested fractions exhibited lower cytotoxicity toward HEK-293 cells under the applied conditions; however, claims of selectivity should be confirmed using additional normal or primary cell models. Overall, the findings clarify the role of extraction strategy, harvest stage and targeted fractionation in linking phenolic composition with biological activity. Full article

Cancer therapy remains limited by drug resistance and poor selectivity, while inflammation-driven tumor progression further complicates treatment outcomes. Antimicrobial peptides (AMPs) have emerged as promising therapeutic alternatives due to their multifunctional properties. In this study, we investigated the anticancer and immunomodulatory activities of KI17, a rationally designed peptide derived from GL18, a peptide fragment identified from the talisin protein of Talisia esculenta. KI17 exhibited dose-dependent antiproliferative effects against murine and human melanoma (B16F10-Nex2, SK-MEL-2, A375) and cervical cancer (HeLa) cell lines, while displaying reduced cytotoxicity toward non-tumoral BV-2 microglial cells, resulting in a favorable selectivity index. Mechanistic analyses revealed that KI17 induces morphological alterations, mitochondrial dysfunction, caspase activation, and late-stage apoptosis, together with G0/G1 cell cycle arrest accompanied by accumulation of the Sub-G0 population, indicating coordinated regulation of cell death and cell cycle progression. KI17 effectively suppressed lipopolysaccharide (LPS)-induced microglial activation, markedly reducing pro-inflammatory cytokine and nitric oxide production without compromising cell viability. These biological activities are consistent with the peptide’s optimized physicochemical features, including increased cationicity, amphipathicity, and α-helical folding. Overall, our findings demonstrate that KI17 combines selective anticancer activity with potent immunomodulatory effects, highlighting its potential as a bioinspired peptide for further preclinical development in cancer therapy. Full article