Search Results (12,522)

Background/Objectives: Ascorbic acid (AA)is a micronutrient with concentration-dependent anticancer properties, acting either as a reactive oxygen species (ROS) scavenger or inducer. Methods: Conventional redox-based assays such as MTS/MTT often overestimate cell proliferation due to AA’s interaction with tetrazolium salts, leading to increased formazan production. To overcome this limitation, we employed the Propidium Iodide Triton X-100 (PI/TX-100) assay to evaluate AA’s cytotoxic effects across a diverse panel of cancer and normal cell lines, including prostate (22Rv1, C4-2B, DU-145, LNCaP), breast (MCF-7, MDA-MB-231, MDA-MB-453), lung (A549), liver (HepG2, SK-HEP-1, Huh7), and kidney (Vero) cells. Results: AA significantly suppressed cancer cell viability compared to normal cells (RWPE1 and Vero), with the strongest effects observed in hormone receptor-positive lines. The relative sensitivity to AA followed distinct patterns within each cancer type. Mechanistically, AA-induced cell death involved ROS generation, lipid peroxidation, cell cycle arrest, ferroptosis, apoptosis, and downregulation of pyruvate dehydrogenase kinase 1 (PDHK1). Conclusions: These findings further support the potential of AA as a selective anticancer agent and highlight the importance of assay choice in evaluating its therapeutic efficacy. Full article

Breast cancer is a common and chronic condition, and despite improvements in diagnosis, treatment, and prevention, the number of cases of breast cancer is rising annually. New therapeutic drugs that target specific checkpoints should be created to fight breast cancer. Mandragora autumnalis possesses substantial cultural value as a herb and is regarded as one of the most significant medicinal plants; however, little is known about its anticancerous biological activity and chemopreventive molecular pathways against the triple-negative breast cancer (MDA-MB-231) cell line. In this study, the antioxidant, anticancer, and underlying molecular mechanisms of the Mandragora autumnalis ethanolic leaves extract (MAE) were evaluated, and its phytochemical composition was determined. Results indicated that MAE diminished the viability of MDA-MB-231 cells in a concentration- and time-dependent manner. Although MAE exhibited 55% radical scavenging activity at higher concentrations in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, the attenuation of its cytotoxic effects in MDA-MB-231 cells with N-acetylcysteine (NAC) co-treatment suggests a potential role of oxidative stress. Additionally, MAE caused an increase in the tumor suppressor p53. Moreover, this extract caused a significant decrease in the expression of Ki-67 (a cellular proliferation marker), MMP-9 (matrix metalloproteinase-9, an enzyme involved in extracellular matrix degradation and metastasis), and STAT-3 (a transcription factor regulating cell growth and survival). Also, MAE altered cell cycle, cell migration, angiogenesis, invasion, aggregation, and adhesion to suppress cellular processes linked to metastasis. All of our research points to MAE’s potential to function as an anticancer agent and opens up new possibilities for the development of innovative triple-negative breast cancer treatments. Full article

The plants from the Ocimum genus, belonging to the Labiatae family, serve as important bioresources of essential oils (EOs) rich in biologically active secondary metabolites, widely used in medicine, food, and cosmetics. This study explored the volatile composition, enantiomeric distribution, and in vitro biological activities of EOs from three Ocimum species native to Nepal: O. tenuiflorum L., O. basilicum L., and O. americanum L. EOs were extracted via hydro-distillation and analyzed using gas chromatography–mass spectrometry (GC-MS) for chemical profiling and chiral GC-MS for enantiomeric composition. Hierarchical cluster analysis was performed for major chemotypes. Antioxidant activity was assessed using DPPH and ABTS assays. Antimicrobial efficacy was evaluated using the microbroth dilution method, and cytotoxicity was tested on NIH-3T3 (normal) and MCF-7 (breast cancer) cell lines via the Cell Counting Kit-8 assay. EO yield was highest in O. tenuiflorum (1.67 ± 0.13%) during autumn and lowest in O. americanum (0.35 ± 0.02%) during winter among all Ocimum spp. The major compounds identified in O. tenuiflorum were eugenol (32.15–34.95%), trans-β-elemene (29.08–32.85%), and β–caryophyllene (19.85–21.64%). In O. americanum, the major constituents included camphor (51.33–65.88%), linalool (9.72–9.91%), germacrene D (7.75–1.83%), and β–caryophyllene (6.35–3.97%). For O. basicilum, EO was mainly composed of methyl chavicol (62.16–64.42%) and linalool (26.92–27.05%). The oxygenated monoterpenes were a dominant class of terpenes in the EOs except for O. tenuiflorum (sesquiterpene hydrocarbon). A hierarchical cluster analysis based on the compositions of EOs revealed at least three different chemotypes in Ocimum species. Chiral GC-MS analysis revealed β-caryophyllene and germacrene D as enantiomerically pure, with linalool consistently dominant in its levorotatory form. O. tenuiflorum exhibited the strongest antimicrobial activity, particularly against Candida albicans, and showed notable anticancer activity against MCF-7 cells (IC₅₀ = 23.43 µg/mL), with lower toxicity to normal cells. It also demonstrated the highest antioxidant activity (DPPH IC₅₀ = 69.23 ± 0.10 µg/mL; ABTS IC₅₀ = 9.05 ± 0.24 µg/mL). The EOs from Ocimum species possess significant antioxidant, antimicrobial, and cytotoxic properties, especially O. tenuiflorum. These findings support their potential application as natural agents in medicine, food, and cosmetics, warranting further validation. Full article

Early-onset colorectal cancer (EOCRC) is emerging as a significant global health concern, particularly among individuals under the age of 50. This alarming trend has coincided with an increase in the consumption of processed foods that often rely heavily on synthetic preservatives. At the same time, these additives play a critical role in ensuring food safety and shelf life. Growing evidence suggests that they may contribute to adverse gut health outcomes, which is a known risk factor in colorectal cancer development. At the same time, synthetic preservatives serve essential roles such as preventing microbial spoilage, maintaining color, and prolonging shelf life. Natural preservatives, on the other hand, not only provide antimicrobial protection but also exhibit antioxidant and anti-inflammatory properties. These contrasting functions form the basis of current discussions on their safety and health implications. Despite their widespread use, the long-term health implications of synthetic preservatives remain inadequately understood. This review synthesizes recent clinical, epidemiological, mechanistic, and toxicological data to examine the potential link between synthetic food preservatives and EOCRC. Particular focus is placed on compounds that have been associated with DNA damage, gut microbiota disruption, oxidative stress, and chronic inflammation, which are the mechanisms that collectively increase cancer risk. In contrast, natural preservatives derived from plants and microbes are gaining attention for their antioxidant, antimicrobial, and possible anti-inflammatory effects. While these alternatives show promise, scientific validation and regulatory approval remain limited. This review highlights the urgent need for more rigorous, long-term human studies and advocates for enhanced regulatory oversight. It advocates for a multidisciplinary approach to developing safer preservation strategies and highlights the importance of public education in making informed dietary choices. Natural preservatives, though still under investigation, may offer a safer path forward in mitigating EOCRC risk and shaping future food and health policies. Full article

Gynura procumbens is a commonly adopted medicinal plant native to the tropical regions of East and Southeast Asia and is well recognized for its significant therapeutic potential. Traditionally used in herbal medicine, it has been employed to manage various conditions, including hypertension, diabetes, renal disorders, constipation, and inflammation. Its leaves are particularly rich in flavonoids—such as astragalin, kaempferol, quercetin, myricetin, and rutin—which are associated with anti-glycaemic, anticancer, antihypertensive, antimicrobial, and antioxidant activities. These bioactive constituents form the basis of the broad pharmacological profile of the plant. Emerging studies also suggest a potential role for G. procumbens in the management of infertility, further broadening its therapeutic scope. This review provides a concise overview of its phytochemical constituents, taxonomic classification, and current pharmacological evidence, highlighting its potential as a valuable candidate for novel drug development. Full article

Background: Acacia catechu is an important traditional medicinal plant that has been used to manage several ailments. Many in vitro and in vivo studies have demonstrated that it exhibits chemopreventive and antineoplastic effects by modulating diverse signaling pathways and molecular targets involved in cancer progression. This review attempts to systematically investigate the anticancer mechanisms of A. catechu, encompassing antiapoptotic, antioxidant, and antiproliferative activities. Material and Methods: This review was conducted using scientific databases such as Scopus, Web of Science, and Google Scholar, covering the studies from 2000 to 2024. The PRISMA methodology was applied, using the keywords A. catechu, phytoconstituents, and cancer. Results: A total of 39 studies were compiled from various databases that cited the biological use of A. catechu. The plant has an abundance of phenolic compounds, including catechin, epicatechin, epigallocatechin-3-O-gallate, and epicatechin-3-O-gallate, which show strong anticancer activities. The anticancer potential of A. catechu is explained as it regulates several modulators like reactive oxygen species and cytokines, and downregulates oncogenic molecules like c-myc and various signaling pathways, such as c-Jun and NF-κB. Conclusions: Our findings suggest that A. catechu and its bioactive constituents have the potential for cancer prevention and therapy. However, further mechanistic investigations using pure compounds, along with preclinical and clinical trials, are essential to translate this potential into clinical applications. Full article

Background and Objectives: Metformin, a staple in diabetes care, has recently emerged as a candidate chemotherapeutic agent. In vitro studies suggest that metformin inhibits cancer growth by altering cellular metabolism and enhancing immune responses. Clinical observations further indicate that it suppresses key tumor-promoting pathways such as mTOR and STAT3. This review critically evaluates the therapeutic potential of metformin in oncology through the lens of precision medicine. This review integrates evidence from molecular mechanisms, clinical studies, biomarker-driven trial designs, and the regulatory challenges that continue to delay its approval for oncologic use. Methods: A structured literature search (2015–2025) identified 63 relevant studies, including preclinical, clinical, and translational research. Conclusions: Although metformin shows consistent anticancer effects in laboratory and animal models, its clinical benefits in patients are variable. This inconsistency is likely due to tumor heterogeneity and a lack of biomarker-based patient selection in trials. Targeting these shortcomings through biomarker-enriched, tumor-specific clinical trials is essential to define metformin’s role as a repurposed agent in precision oncology. Full article

Stachys duriaei (Lamiaceae) remains unexplored despite its pharmacological potential. In this study, for the first time, the antiproliferative, pro-apoptotic, cell cycle arrest, and vasorelaxant effects of the n-butanolic extract (BESD) and a VLC fraction (BF1SD) of Stachys duriaei were investigated. Antiproliferative activity was evaluated on PC3 and MDA-MB-231 cell lines via MTT assay (72 h). Apoptosis (Annexin V-FITC/PI) and cell cycle arrest (PI/RNase) were assessed by flow cytometry (24 h, 250–1000 µg/mL). Vasorelaxant effects were studied ex vivo on rat aortic rings. LC-HRMS/MS was used for phytochemical analysis. BESD showed higher antiproliferative activity (IC₅₀: 196 ± 6 µg/mL for PC3, 182 ± 8 µg/mL for MDA-MB-231) than BF1SD (IC₅₀: 281 ± 6 µg/mL and 273 ± 3 µg/mL, respectively). Apoptosis was dose-dependent, with BF1SD displaying a stronger effect at 1000 µg/mL (67.3 ± 0.5% vs. 49.9 ± 0.7% for BESD). BESD induced G2/M arrest, while BF1SD caused G0/G1 and G2/M arrest. Vasorelaxation was endothelium-dependent, likely mediated by NO. Identified compounds (hyperoside, luteolin-7-glucoside, and rutin) may contribute to these effects. BESD and BF1SD exhibit anticancer and vasorelaxant properties, indicating potential therapeutic use against cancer and cardiovascular diseases. Further studies are needed to isolate active compounds and confirm their effects in vivo. Full article

Background/Objectives: Systemic toxicities to key organs like the heart, liver, and kidneys impair the efficacy of chemotherapy in cancer treatment. These toxicities are caused by oxidative stress, inflammation, mitochondrial malfunction and ferroptosis, causing clinical morbidity and possibly impaired adherence to treatment. This review, also, examines how magnesium, selenium, zinc and vitamin D protect against chemotherapy-induced cardiotoxicity, hepatotoxicity and nephrotoxicity. Methodology: A complete literature search of PubMed (MEDLINE), Scopus, Cochrane Library and Embase was used to synthesize data till 29 June 2025. Studies included randomized and non-randomized trials, cohort studies, case series (≥3 patients), and relevant systematic reviews. To contextualize pathways, preclinical in vivo and in vitro studies were studied independently. Patients undergoing systemic chemotherapy and magnesium, selenium, zinc or vitamin D therapies were eligible. Supplementation’s safety and organ-specific toxicity were investigated. Results: Magnesium protected against cisplatin-induced nephrotoxicity via modulating renal transporters and oxidative defenses across chemotherapy regimens. Selenium supplementation has strong antioxidant and anti-inflammatory characteristics, especially in avoiding cardiac and hepatic injury, although its nephroprotective potential was formulation-dependent. Zinc’s activity was connected to metallothionein-mediated redox stabilization, inflammatory regulation, and cardiac and hepatic resilience. Vitamin D and its analogs reduced cardiotoxicity and nephrotoxicity through mitochondrial preservation and immunomodulatory signaling. Conclusions: To date, magnesium, selenium, zinc, and vitamin D have been shown to reduce chemotherapy-related organ toxicities. Preclinical studies are promising, but randomized clinical trials are needed to prove therapeutic effectiveness and oncologic safety. Full article

Background: Avicennia marina (Forsk.) Vierh., a widely distributed mangrove species, is known for its diverse secondary metabolites with potential pharmacological applications. Despite its dominance in the Arabian Gulf, where A. marina may have adapted to extreme environmental conditions with a distinct set of bioactive molecules, research in this region remains limited. Methods: This study investigates the phytochemical composition, antioxidant activity, and in vitro cytotoxicity of extracts from different plant parts, including roots, leaves, propagules, pericarps, and cotyledons, collected in the United Arab Emirates (UAE). Extracts were analyzed using ultra-pressure liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS). Antioxidant activity was assessed using DPPH and ABTS assays, while cytotoxicity was evaluated against human cancer and normal cell lines. Results: Analysis revealed 49 compounds, including iridoid glycosides, hydroxycinnamic acids, phenylethanoid glycosides, flavonoid glycosides, and triterpene saponins, several reported for the first time in A. marina and mangroves. The pericarp and root extracts exhibited the highest scavenging activity (DPPH: 187.14 ± 2.87 and 128.25 ± 1.12; ABTS: 217.16 ± 2.67 and 147.21 ± 2.42 μmol TE/g, respectively), correlating with phenylethanoid content. The root extract also displayed the highest cytotoxicity, with IC₅₀ values of 58.46, 81.98, and 108.10 μg/mL against MDA-MB-231, SW480, and E705, respectively. In silico analysis identified triterpene saponins as potential contributors. Conclusions: These findings highlight the root extract of A. marina as a promising source of bioactive compounds with potential antioxidant and anticancer applications, supporting further exploration for novel therapeutic candidates. Full article

Agarwood, valued for its resin, has long been used in perfumery, incense, and traditional medicine. Its resin is primarily derived from species of Aquilaria and is produced through a still-unknown process in response to biotic or abiotic stress. Concerns regarding agarwood’s sustainability and conservation have emerged because of the substantial loss of natural resources due to overharvesting and illegal trade. To address these concerns, artificial techniques are being used to produce agarwood. The mechanism underlying agarwood production must be elucidated to enhance yield. The authentication of agarwood species is challenging because of morphological similarities between pure and hybrid Aquilaria species. Techniques such as DNA barcoding, molecular marker assessment, and metabolomics can ensure accurate identification, facilitating conservation. Artificial intelligence and machine learning can support this process by enabling rapid, automated identification on the basis of genetic and phytochemical data. Advances in resin induction methods (e.g., fungal inoculation) and chemical induction treatments are improving yield and quality. Endophytic fungi and bacteria promote resin production at minimal harm to the tree. Agarwood’s pharmacological potential—antimicrobial, anti-inflammatory, and anticancer effects—has driven research into bioactive compounds such as sesquiterpenes and flavonoids for the development of novel drugs. This systematic review synthesized current evidence on species authentication, induction techniques, and pharmacological properties. The findings may guide future research aimed at ensuring sustainable use and enhancing the medicinal value of agarwood. Full article

Carbonic anhydrase IX (CA IX) is a transmembrane metalloenzyme that is increased in tumor cells under hypoxia and plays an important role in solid tumor acidification. It is a marker of tumor hypoxia and a prognostic factor in human malignancies. Given the critical role of CA IX and their over expression in many cancer tissues, they have emerged as a promising target for developing novel anticancer therapeutics. In this study we designed a pharmacophore model based on known inhibitors to screen small compound libraries to discover potential inhibitors of CA IX. Molecular docking experiments discovered that four compounds ZINC613262012, ZINC427910039, ZINC616453231, and DB00482 exhibited a strong binding affinity towards CA IX, mimicking the interaction pattern similar to native inhibitors. Molecular dynamics simulations and an MM-PBSA analysis revealed ZINC613262012, ZINC427910039, and DB00482 as the most potential and stable inhibitors with the binding free energies −10.92, −18.77, and −12.29 kcal/mol, respectively. In addition, DFT-based analyses supported their favorable electronic properties, further validating their potential as CA IX inhibitors. These three hits demonstrated a greater stability and compactness relative to the known inhibitors, suggesting these might be used CA IX inhibitors to treat tumors. Full article

Rugulopteryx okamurae is an invasive brown alga that has colonised Mediterranean and northeastern Atlantic coastlines, posing significant ecological and economic challenges. Its biomass is rich in structurally diverse metabolites—including polysaccharides (alginate, fucoidan, laminaran), phlorotannins, diterpenoids, fatty acids, and peptides—many of which exhibit notable antioxidant, anti-inflammatory, antimicrobial, and anticancer activities. Comparative assessment of extraction yields, structural features, and bioactivity data highlights phlorotannins and diterpenoids as particularly promising, demonstrating low-micromolar potencies and favourable predicted interactions with key inflammatory and apoptotic targets. Algal polysaccharides exhibit various bioactivities but hold strong potential for scalable and sustainable industrial applications. Emerging compound classes such as fatty acids and peptides display niche bioactivities; however, their structural diversity and mechanisms of action remain insufficiently explored. Insights from in vitro and in silico studies suggest that phlorotannins may modulate NF-κB and MAPK signalling pathways, while diterpenoids are implicated in the induction of mitochondrial apoptosis. Despite these findings, inconsistent extraction methodologies and a lack of in vivo pharmacokinetic and efficacy data limit translational potential. To overcome these limitations, standardized extraction protocols, detailed structure–activity relationship (SAR) and pharmacokinetic studies, and robust in vivo models are urgently needed. Bioactivity-guided valorisation strategies, aligned with ecological management, could transform R. okamurae biomass into a sustainable source for functional foods, cosmetics, and pharmaceuticals applications. Full article

Fermentation represents a sustainable biotechnological approach for enhancing bioactive properties of plant-based foods, yet its anticancer effects remain underexplored. We evaluated the antiproliferative activity of fermented (with commercial probiotic lactic acid bacteria consortium) and unfermented plant-based beverages derived from tiger nut, carob, and rice using an in vitro model. Following INFOGEST 2.0 gastrointestinal digestion, bioaccessible fractions were applied to Caco-2 colorectal adenocarcinoma cells at 1:15 v/v dilution for 24 h. Analyses included cell viability, apoptosis detection, cell cycle distribution, reactive oxygen species production, glutathione content, mitochondrial membrane potential, and intracellular calcium levels. Fermented tiger nut achieved superior (p < 0.05) cytotoxicity compared to unfermented counterpart (39.6% vs. 77.4% cell viability) through dual mechanisms: depleting cellular antioxidant defenses (glutathione reduced to 55.9%) while inducing oxidative stress (180.3% ROS overproduction). This evoked irreversible apoptosis (76.9% early apoptosis) and extensive DNA fragmentation (84.8% SubG₁ population) via calcium-independent pathways. Fermented carob operated through cytostatic mechanisms, inducing G₀/G₁ cell cycle arrest (74.7% vs. 44.2% in blank digestion cells) without oxidative stress. Fermentation reduced (p < 0.05) rice beverage antiproliferative activity (90.2% vs. 71.9% unfermented beverage cell viability). These findings establish lactic acid fermentation as effective for developing plant-based beverages with anticancer mechanisms, offering dietary strategies for colorectal cancer prevention. Full article

Background: Histone deacetylase 6 (HDAC6) is a unique class IIb HDAC isozyme characterized by two catalytic domains and a zinc finger ubiquitin-binding domain. It plays critical roles in various cellular processes, including protein degradation, autophagy, immune regulation, and cytoskeletal dynamics. Due to its multifunctional nature and overexpression in several cancer types, HDAC6 has emerged as a promising therapeutic target. Methods: In this study, we employed a ligand-based pharmacophore modeling approach using a structurally diverse set of known HDAC6 inhibitors. This was followed by the virtual screening of over 140,000 commercially available compounds from both the MolPort and Asinex databases. The screening workflow incorporated pharmacophore filtering, molecular docking, and molecular dynamic (MD) simulations. Binding free energies were estimated using Molecular Mechanics Generalized Born Surface Area (MM-GBSA) analysis to prioritize top candidates. A fluorometric enzymatic assay was used to measure HDAC6 activity, while cell viability assay by Cell Titer Glo was used to assess the anti-tumor activity against drug-sensitive and -resistant multiple myeloma (MM) cells. Western blotting was used to evaluate the acetylation of tubulin or histone H4 after treatment with selected compounds. Results: Three promising compounds were identified based on stable binding conformations and favorable interactions within the HDAC6 catalytic pocket. Among them, Molecular Mechanics Generalized Born Surface Area (MM-GBSA) analysis identified Compound 10 (AKOS030273637) as the top theoretical binder, with a ΔG_bind value of −45.41 kcal/mol. In vitro enzymatic assays confirmed its binding to the HDAC6 catalytic domain and inhibitory activity. Functional studies on MM cell lines, including drug-resistant variants, showed that Compound 10 reduced cell viability. Increased acetylation of α-tubulin, a substrate of HDAC6, likely suggested on-target mechanism of action. Conclusions: Compound 10, featuring a benzyl 4-[4-(hydroxyamino)-4-oxobutylidene] piperidine-1-carboxylate scaffold, demonstrates potential drug-like properties and a predicted bidentate zinc ion coordination, supporting its potential as an HDAC6 inhibitor for further development in hematologic malignancies. Full article