Search Results (188)

Bladder cancer remains a major clinical challenge because of its high recurrence rate, marked molecular heterogeneity, frequent progression, and limited durability of current therapeutic strategies. Increasing evidence indicates that acetylation, as a reversible and druggable epigenetic modification, plays a central role in bladder cancer biology by linking chromatin remodeling to transcriptional regulation, DNA damage repair, metabolic adaptation, and immune modulation. Both histone and non-histone acetylation are frequently dysregulated in bladder cancer, and these alterations contribute to multiple malignant phenotypes, including sustained proliferation, defective cell-cycle control, apoptosis evasion, epithelial–mesenchymal transition, metastatic progression, and therapeutic resistance. In this review, we summarize the mechanistic basis of acetylation imbalance in bladder cancer, with particular emphasis on the roles of histone acetyltransferases, histone deacetylases, sirtuins, and acetylation-associated metabolic regulators. We further discuss the emerging evidence that natural products can modulate acetylation-related pathways in bladder cancer, mainly through targeting HDAC-dependent histone deacetylation and SIRT1-associated non-histone deacetylation. Representative compounds, including sulforaphane, erucin, puerarin, capsaicin, curcumin, trichostatin A, trichostatin C, and pinocembrin, highlight the potential of natural products to suppress tumor growth, promote apoptosis, impair migration, and enhance antitumor immunity through acetylation-related mechanisms. Beyond summarizing individual agents, the evidence was evaluated based on the integration of acetylation-related target engagement, acetylation remodeling, and bladder cancer-relevant phenotypic outcomes. The current evidence is heterogeneous. SFN/ECN, capsaicin, and pinocembrin offer the most convincing bladder cancer-specific support, whereas several other compounds remain limited by context-dependent effects, indirect pathway inference, or incomplete validation of the proposed acetylation mechanisms. These findings support an evidence-oriented translational framework that prioritizes natural products according to mechanistic robustness, bladder cancer specificity, and combination potential. Overall, acetylation-targeting natural products represent a promising but still evolving therapeutic strategy for bladder cancer, warranting further subtype-specific, mechanistically rigorous, and translationally oriented investigation. Full article

Breast cancer treatment remains challenging due to therapeutic resistance and the limited availability of effective molecular targets. We investigated the anticancer effects of sulforaphane (SFN) and broccoli sprout extract (BSE), an SFN-enriched phytochemical formulation, in MCF7 and MDA-MB-231 breast cancer cells. Cell viability, colony formation, and apoptotic responses were evaluated using standard in vitro assays, and underlying mechanisms were examined by flow cytometry and Western blot analysis. BSE and SFN reduced cell viability in a dose-dependent manner, suppressed anchorage-independent growth, and induced apoptosis associated with increased reactive oxygen species (ROS) generation and activation of c-Jun N-terminal kinase and p38 MAPK signaling pathways. These effects were accompanied by mitochondrial depolarization, G2/M cell cycle arrest, and caspase activation. Pharmacokinetic analysis in rats demonstrated that oral administration of BSE resulted in sustained, dose-dependent systemic exposure to SFN. Consistent with these findings, oral BSE significantly inhibited tumor growth in breast cancer xenograft models. Collectively, these results indicate that BSE exerts anticancer effects through coordinated modulation of ROS-associated MAPK signaling, mitochondrial dysfunction, and apoptotic pathways, and may serve as a promising orally administered SFN-containing phytochemical formulation that may function as a delivery matrix for breast cancer management. Full article

Cancer therapy is increasingly shaped by the need for agents that are both mechanistically precise and clinically tolerable. Sulforaphane (SFN), a dietary isothiocyanate enriched in cabbage-family vegetables such as cauliflower and Brussels sprouts, has emerged as a pleiotropic modulator of tumor biology. This review synthesizes current evidence that SFN regulates diverse cancer-relevant processes, including redox homeostasis, cell-cycle progression, apoptosis, autophagy and epigenetic remodeling, largely through coordinated effects on transcriptional (for example, Nrf2, MAPK, NF-κB and AP-1), post-transcriptional (microRNAs and messenger RNAs) and epigenetic (DNA methyltransferases and histone deacetylases) networks. We then examine how functional nucleic acids, including aptamers, small interfering RNAs, microRNAs and tetrahedral DNA nanostructures, can be engineered to guide SFN to tumor cells, amplify pathway-specific effects and overcome resistance. Particular emphasis is placed on nanotechnology-enabled delivery platforms that enhance SFN stability, bioavailability and tumor selectivity. Finally, we outline key challenges, such as context-dependent Nrf2 activity, inter-individual variability in metabolism and incomplete clinical validation, and propose priorities for translating SFN-based functional nucleic acid systems into rational, combination-ready strategies for precision oncology. Full article

Background/Objectives: Diabetic foot ulcers (DFUs) are a common and challenging complication of diabetes, significantly impacting the quality of life for patients due to impaired wound healing. Exploring effective and targeted therapies for DFUs is therefore both important and meaningful. Sulforaphane (SFN), a natural bioactive compound found in cruciferous vegetables, shows promise in this area. However, its role and underlying mechanisms in promoting wound healing in DFUs have not been fully understood. Methods: Human umbilical vein endothelial cells (HUVECs) were cultured under high-glucose conditions to establish an in vitro diabetic model. Cell viability, inflammation, apoptosis, and mitochondrial function were assessed. The expression and activation of Nrf2 were examined following SFN treatment. Additionally, Nrf2 overexpression was performed to validate its role in mediating the protective effects of SFN under high-glucose stress. Results: High-glucose conditions significantly reduced HUVEC viability and increased inflammation, apoptosis, and mitochondrial dysfunction. Treatment with SFN effectively counteracted these detrimental effects. SFN robustly activated Nrf2 signaling, and overexpression of Nrf2 recapitulated the protective effects of SFN, attenuating cellular damage under high-glucose conditions. Conclusions: SFN activates Nrf2 expression and protects HUVECs from high-glucose-induced injury by improving cell viability, mitochondrial function, and inflammatory response. These findings suggest that SFN may serve as a promising targeted therapy for diabetic foot ulcers. Full article

Background/Objectives: Glucosinolates (GSLs) from cruciferous vegetables (CVs), sulfur (S)- and nitrogen-containing compounds, are enzymatically hydrolyzed by myrosinase (EC 3.2.1.147) to yield bioactive derivatives such as isothiocyanates (ITCs) and indoles. These metabolites exhibit chemopreventive and anticancer properties. The article compiles evidence regarding the following: (i) the molecular mechanisms regulating the biosynthesis of key derivatives, including sulforaphane (SFN), phenethyl isothiocyanate (PEITC), and indole-3-carbinol (I3C); (ii) epidemiological and clinical findings; and (iii) strategies to link plant science with nutritional interventions for cancer prevention. Methods: An integrative literature review was conducted using Web of Science, Scopus, ScienceDirect, Google Scholar, and PubMed. English-language studies addressing mechanistic insights, nutritional factors, epidemiology, and clinical trials were included. Results: The biosynthesis and metabolism of GSL in plants are regulated by S and several transcription factors that promote or repress GSL production. Additionally, food processing has been shown to influence retention time and the formation of ITCs. In humans, ITCs activate nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated detoxification, induce apoptosis, and modulate epigenetic pathways. Epidemiological data show inverse associations between CV intake and cancer risk, though variability exists. Clinical trials have confirmed the bioavailability and effects of glucoraphanin and SFN on cancer-related biomarkers. Conclusions: The described compounds are bioavailable in humans and modulate the clinically relevant pathways linked to carcinogenesis. Larger, standardized interventions are needed to determine effective intake levels, optimize bioavailability, and define their potential role in evidence-based nutritional strategies for cancer prevention. Full article

Sulforaphane (SFN), an aliphatic isothiocyanate derived from cruciferous vegetables such as broccoli, has emerged as a chemopreventive dietary agent. SFN exerts multifaceted anticancer effects through the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)–antioxidant response element (ARE) pathways, inhibition of histone deacetylases (HDACs) and hypoxia-inducible factor-1α (HIF-1α), and regulation of apoptosis and autophagy. Epidemiological studies have consistently associated cruciferous vegetable intake with reduced cancer risk, while mechanistic research has elucidated the capacity of SFN to modulate redox balance, detoxification pathways, and epigenetic processes. Recent clinical trials have further demonstrated its potential to reduce carcinogenic biomarker levels and support metabolic detoxification. This review integrates evidence from epidemiological observations, molecular mechanisms, and clinical studies to provide a comprehensive understanding of the role of SFN in cancer prevention and therapy. Finally, translational challenges, including limited bioavailability, dose optimization, and standardization of broccoli-derived preparations, are discussed as critical factors for successfully translating SFN therapies from bench to bedside. Full article

Background: Alcohol is associated with increased mortality and morbidity globally. Pulmonary infections with opportunistic pathogens can occur in healthy humans; however, binge alcohol intoxication (≥0.08% BAC) is a major risk factor. We have previously shown that a single dose of alcohol comparable to binge alcohol intoxication increases infection by reducing alveolar macrophage function in vivo. Sulforaphane (SFN), a phytonutrient, is a potent inducer of antioxidant production through the induction of nuclear factor erythroid 2-related factor 2 (Nrf2) and inhibition of the nuclear factor kappa-light-chain-enhancer (NF-kB) pathway. The aim of this study was to test the therapeutic potential of SFN given as a pretreatment to prevent alcohol-induced phagocytic dysfunction. Methods: Intracellular phagocytic killing was measured via colony-forming units (CFU) and cytokine expression via ELISA. G. mellonella survival was used to determine the therapeutic potential of SFN in vivo. Results: Dose–response curves indicated that SFN concentrations of less than 20 µM were not cytotoxic in either MH-S (murine) or THP-1 (human) cells. Live infection assay results showed that MH-S and THP-1 cells pretreated with SFN (5 µM) and challenged with 0.2% (v/v) alcohol for 3 or 8 h prior to live B. thailandensis or S. epidermidis infection improved intracellular pathogen killing between 12- and 20-fold compared to macrophages treated with alcohol alone. ELISA analysis indicated that SFN significantly reduced levels of Tumor necrosis factor-alpha (TNF-α) expression at 3 and 8 h compared to controls. Additionally, a Galleria mellonella larvae model demonstrated greater survivability in the prophylaxis group compared to larvae exposed to either Gram-positive or Gram-negative pathogens, as well as in groups that received alcohol prior to pathogen inoculation. Conclusions: Taken together, SFN-induced cytoprotection was extended beyond in vitro cell culture to include an in vivo G. mellonella model demonstrating protection against Gram-positive and negative opportunistic pathogens. These data demonstrate that SFN may be an effective pretreatment option to prevent alcohol-mediated innate immune dysfunction and restore macrophage phagocytic killing. Full article

Ionising radiation-induced lung injury is a major complication of thoracic radiotherapy, primarily driven by oxidative stress and inflammation. The current study evaluates and compares the protective effects of sulforaphane (SFN) and curcumin (CUR) pretreatment against radiation-induced oxidative damage and inflammation in rat lung tissue. Female Wistar rats were pretreated in vivo with SFN (2 mg/kg b.w./day) or CUR (4.13 mg/kg b.w./day) for 28 days per os. Isolated lung tissues were exposed ex vivo to γ-radiation (absorbed dose: 2 Gy). Oxidative stress markers—malondialdehyde (MDA), ischemia-modified albumin (IMA), total sulfhydryl (SH) groups, reduced glutathione (GSH), and superoxide dismutase (SOD)—and inflammatory markers—tumour necrosis factor alpha (TNF-α), prostaglandin-endoperoxide synthase 2 (PTGS2/COX-2), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β)—were measured to evaluate irradiation and protective effects. Radiation significantly increased MDA, TNF-α, PTGS2/COX-2, and IL-6 levels while decreasing SH groups. Pretreatment with SFN or CUR attenuated these changes. CUR showed a more pronounced effect on oxidative stress-related parameters, whereas SFN more strongly influenced inflammatory markers. These findings suggest that SFN and CUR differentially modulate radiation-induced oxidative and inflammatory responses in lung tissue under the applied experimental conditions and warrant further investigation of their potential as protective agents in radiotherapy. Full article

Objective: This study investigated the effects of different doses and timing of sulforaphane (SFN) supplementation on reducing obesity induced by a high-glycemic-index diet (HGID) and on correcting poor glycemic control and dyslipidemia in C57BL/6 mice. Method: For 15 weeks, mice were administered a control diet (control), HGID, HGID + oral 5 mg/kg/day SFN (HGID + LSFN), or HGID + 20 mg/kg/day SFN (HGID + HSFN), and following 15 weeks of HGID, mice were treated with 5 mg/kg/day SFN (PO-HGID + LSFN) or 20 mg/kg/day SFN (PO-HGID + HSFN) for 5 weeks. Results: SFN reduced body weight gain and serum glucose. The lowest levels of HbA1c were observed in the control and HGID + LSFN groups. Mice in the HGID group exhibited impaired glucose clearance and were less sensitive to insulin compared to the control. A remarkable improvement in glucose and insulin tolerance was observed in both PO-HGID + SFN and HGID + SFN groups. Lipid profile parameters and serum insulin levels were found to be lower in the control and HGID + SFN groups compared to the HGID group. SFN increased serum adiponectin levels when administered concurrently with HGID. IRS1 and IRS2 levels were highest in the control and HGID + LSFN groups, and high-dose SFN supplementation suppressed IRS1 independently of timing. Exposure to HGID downregulated the expression of PGC-1α and sirtuins. SIRT1 and SIRT3 gene expressions showed a significant increase at both doses, whereas SIRT2 gene expression increased significantly only at 5 mg/kg/day SFN. FASN expression was upregulated in all HGID-fed groups with or without SFN intervention. Conclusions: SFN may reverse the adverse effects of HGID in a time- and dose-dependent manner by regulating postprandial insulin, inhibiting gluconeogenesis, and enhancing fatty acid oxidation through the activation of sirtuins and PGC-1α. Full article

Oxidative stress from environmental pollutants is linked to chronic degenerative diseases. Research indicates that specific phytochemicals in our diets can reduce and mitigate the harmful effects of pro-oxidant insults on health. However, limited randomized clinical trials show the protective effects of these compounds. This lack of in vivo evidence is partly due to the low bioavailability of these compounds, which can obscure their actual benefits. The present work investigates whether selected dietary phytochemicals are equally effective in activating cellular defense against oxidative stress at low doses. In a previous study, we found that Curcumin (Curc) at a concentration of 1 μM protected human myeloid cells from cytotoxicity induced by pro-oxidant species by activating the expression of Nrf2/ARE-dependent transcripts, including NADPH: quinone oxidoreductase-1 (NQO-1) and heme oxygenase-1 (HO-1). Now, we aim to extend our observation to other natural activators of the Nrf2 pathway, such as Sulforaphane (SFN) and three structurally related molecules belonging to the flavonoid family: Quercetin (Q), Catechin (C), and Fisetin (F). These compounds were applied at low concentrations (1 μM) to assess their antioxidant activity against H₂O₂-induced oxidative stress, their effects on cellular viability, and the capacity to drive the expression of NQO-1/HO-1 in various cellular models. Our findings indicate that low-dose phytochemicals differ in their cytoprotective efficacy, which depends on both dosage and intracellular uptake or metabolism. We propose that only specific natural antioxidants can protect cells from oxidative stress, underscoring the need to clarify the mechanisms behind this selectivity to better design nutraceuticals and functional foods. Full article

Cancer progression is driven not only by biochemical signals but also by abnormal physical forces within a stiffened tumor microenvironment. This review re-examines the anticancer compound sulforaphane (SFN) through the integrative lens of tumor biomechanics. We propose SFN functions as a “mechano-modulator,” whose pleiotropic effects converge to disrupt pro-invasive mechanotransduction. SFN targets key force-sensitive pathways (e.g., YAP/TEAD, Rho/ROCK), destabilizes invasion machinery (cytoskeleton, invadopodia), and promotes tissue-level changes such as extracellular matrix remodeling. While preclinical evidence for this mechano-modulatory role is compelling, this perspective also highlights the critical need for clinical validation and discusses the key translational challenges. By systematically linking SFN’s molecular actions to the biophysics of tumor progression, this synthesis provides a novel framework for understanding its efficacy and outlines a rational path for its future development as a mechano-inspired therapeutic. Full article

The rising global prevalence of obesity and metabolic disorders calls for innovative dietary strategies that can modulate key enzymatic pathways involved in lipid and carbohydrate metabolism. This study uncovers the effects of sulforaphane (SFN)-rich broccoli-derived formulations—including liquid and lyophilised forms, as well as two commercial prototypes, Sulforaphan^® BASIC and Sulforaphan^® SMART, the latter being characterised by the inclusion of an enteric-coated myrosinase enzyme designed to enhance the in situ conversion of glucosinolates (GSL) into bioactive isothiocyanates (ITC)—on lipid and carbohydrate metabolism in 3T3-L1 adipocytes. Across the formulations, total GSL content ranged widely, with GS0 showing the highest levels. Functionally, all SFN-rich formulations significantly reduced intracellular triglyceride content, with the SMART formulation achieving the strongest reduction (11% compared with untreated controls). Across enzymatic assays, we recorded that every formulation inhibited lipoprotein lipase and α-glucosidase activities, with Sulforaphan^® BASIC and Sulforaphan^® SMART leading to moderate inhibition (40–50%). The potent effect of SMART formulation may be associated with the presence of enteric-coated myrosinase, which enhances the conversion of GSL into bioactive ITC. The gathered evidence provides further insights into the potential of bioactive compounds in cruciferous foods to modulate metabolic health, underscoring their potential role in complementary therapeutic strategies for obesity and its comorbidities. Full article

Background: Recent research has focused on diet as a potential source of antioxidants in the context of both human health and disease prevention. Among the many plant-derived antioxidants, sulforaphane (SFN) has emerged as a potent phytochemical in the recent literature for sustaining health and combating cancerous, inflammatory, and neurodegenerative diseases. Thus, the market for supplements and functional foods has been quick to adapt to this new market niche. We aimed to investigate the phytochemical profile of broccoli sprouts and evaluate their antioxidant capacity through biochemical assays. Methods: UHPLC and MS/MS were used to analyse the phytochemical characteristics of broccoli sprout extracts. Antioxidant tests, including the DPPH test, ferrous iron chelation, hydroxyl radical neutralisation, and lipoxygenase inhibition, were used to evaluate their antioxidant potential. Results: The broccoli sprout extracts emerged as an adequate source of SFN, as well as other biologically active compounds such as xanthorhamnin. Moreover, biochemical assays showcased their antioxidant capacity. Conclusions: Broccoli sprouts could constitute an important source of dietary antioxidants with high bioavailability and high accessibility, helping sustain health and even combat various diseases. Full article

DNA methylation holds promise for the early detection of tissue damage, making it crucial for identifying polycyclic aromatic hydrocarbon (PAH)-associated epigenetic biomarkers in childhood asthma. Sulforaphane (SFN), as a potential epigenetic modulator, can alleviate the adverse effects of environmental pollutants. This study quantified serum PAHs in 370 children via gas chromatography–mass spectrometry, assessed the methylation of target genes using bisulfite sequencing PCR (BSP), and performed mediation analysis to estimate the mediating effects of methylation levels between PAHs and childhood asthma. Murine models exposed to PAHs prenatally or postnatally, with offspring challenged with ovalbumin (OVA), were analyzed for lung DNA methylation. In vitro, HBE cells and HBSMCs treated with benzo(a)pyrene (BaP) and/or SFN were tested for inflammatory cytokines, methylation-related enzymes, and matrix metallopeptidase 9 (MMP9) modifications. The results showed total PAHs were associated with childhood asthma, with mediating effects of long interspersed nuclear element-1 (LINE-1) methylation. Prenatal PAH exposure enriched differentially methylated genes in the extracellular matrix (ECM)-receptor interaction pathway, while postnatal exposure enriched those in purine metabolism, and postnatal exposure also elevated Mmp9 expression via hypomethylation. BaP increased the expression of interferon gamma (IFN-γ), interleukin-4 (IL-4), interleukin-17A (IL-17A), transforming growth factor beta 1 (TGF-β), and ten-eleven translocation methylcytosine dioxygenases (TETs), and it upregulated MMP9 via enhancer hypomethylation and H3K27ac enrichment, while SFN reversed these effects by downregulating histone methyltransferase (HMT), leading to reduced H3K4me1 and subsequent H3K27ac depletion, thus suppressing MMP9 transcription. This study demonstrates that DNA methylation mediates PAH–childhood asthma associations, with distinct patterns in different exposure windows; MMP9 could serve as a crucial target for epigenetic modification during lung inflammation induced by PAH exposure, and SFN reverses PAH-induced epigenetic changes, aiding prevention strategies. Full article

Radishes (Raphanus sativus L.) have attracted interest as functional foods containing various bioactive components. Among them, sulforaphane (SFN), an isothiocyanate compound, is known for its potent antioxidant and anticancer properties. This study aimed to extract, purify, and identify SFN and SFN-derived compound X (SFN-DX), a dietary sulfur-containing bioactive compound, from freeze-dried radishes. High-performance liquid chromatography analysis revealed that the freeze-dried radish extract contained 13.262 mg/g SFN-DX. A major peak was detected with a f of 12.713 min, closely matching that of the SFN standard (RT = 12.883 min). SFN-DX was subsequently isolated with 99% purity through preparative liquid chromatography. Structural elucidation confirmed that SFN-DX is a derivative of SFN and shares characteristic features with isothiocyanates. The storage stability of purified SFN-DX was evaluated under various temperatures (−18 °C, 4 °C, 20 °C, and 40 °C) and storage durations (1 week and 1 month). A significant reduction in compound purity was observed at elevated temperatures and during prolonged storage. Accordingly, −18 °C was identified as the optimal storage temperature for preserving the stability of SFN-DX. Collectively, these findings provide a scientific basis for the efficient extraction, structural analysis, and storage of dietary sulfur-containing compounds derived from radishes. Full article