Search Results (1,336)

Claoxylon longifolium (Euphorbiaceae) is an indigenous vegetable that has been used in southern Thai traditional medicine and cuisine. A bioassay-guided approach was adopted to investigate the phytochemicals and chemopreventive potential of C. longifolium leaves and stems. Phytochemical investigation of the active MeOH fractions afforded six known compounds, including caffeic acid (1), isovitexin (2), and vicenins 1–3 (3–5) from leaves and hexadecanoic acid methyl ester (6) from stems. Their structures were determined by spectroscopic means. Ten constituents were tentatively identified from the oily fractions of stems by GC-MS. Non-cytotoxic concentrations of compounds 1–6 were identified using the MTT cell viability assay. The ability of compounds 1–6 at non-cytotoxic concentrations to induce Nrf2 activation, correlating to their potential chemopreventive properties, was determined using a luciferase reporter assay in the AREc32 cell line. Only vicenin 1 (3) was considered to be a potent chemopreventive compound, as it increased luciferase activity by 2.3-fold. In silico studies on compounds 2–5 and vitexin (16) revealed the potential of these compounds as cancer chemopreventive and chemotherapeutic agents. This study provides the first report on the chemopreventive properties of C. longifolium. All identified and isolated compounds are reported here for the first time from this species. Full article

Dark sweet cherries (DSC) phytochemicals have emerged as a promising dietary strategy to combat triple-negative breast cancer (TNBC). This study explored the effects of DSC extract rich in anthocyanins (ACN) as a chemopreventive agent and as a complement to doxorubicin (DOX) in treating TNBC tumors and metastasis using a 4T1 syngeneic animal model. Initiating ACN intake as a chemopreventive one week before 4T1 cell implantation significantly delayed tumor growth without any signs of toxicity. Both DOX treatment and the combination of DOX-ACN effectively delayed tumor growth rate, but DOX-ACN allowed for body weight gain, which was hindered by DOX alone. As a chemopreventive, ACN downregulated metastasis- and immune-suppression-related genes, including STAT3, Snail1, mTOR, SIRT1, TGFβ1, IKKβ, and those unaffected by DOX alone, such as HIF, Cd44, and Rgcc32. Correlations between mRNA levels seen in control and DOX groups were absent in ACN and/or DOX-ACN groups, indicating that Cd44, mTOR, Rgcc32, SIRT1, Snail1, and TGFβ1 may be ACN targets. The DOX-ACN treatment showed a trend toward enhanced efficacy involving CREB, PI3K, Akt-1, and Vim compared to DOX alone. Particularly, ACN significantly suppressed lung metastasis compared to the other groups. ACN also decreased the frequency and incidence of metastasis in the liver, heart, kidneys, and spleen, while their metastatic area (%) and number of breast cancer (BC) metastatic tumor nodules were lowered without reaching significance. Further research is needed to explore the efficacy of combining ACN with drug therapy in the context of drug resistance. Full article

Estrogens are considered the most important risk factor for the development of breast cancer. Therefore, attempts are being made to reduce their level through diminished synthesis on one hand and to protect against the formation of DNA-damaging estrogen metabolites on the other. Cytochromes P450 (CYPs) play key roles in estrogen synthesis and catabolism, leading to potentially carcinogenic metabolites. CYP19 (aromatase) catalyzes the conversion of androgens to estrogens. The estrogen receptor-dependent pathway induces cell growth. CYP1 family enzymes, particularly CYP1B1, are involved in the redox cycling of estrogen metabolites and the subsequent estrogen–DNA adducts formation. Naturally occurring phytochemicals of different classes were shown to modulate the CYP expression and activity in cell-free systems or breast cancer cells. One of the most promising CYP19 inhibitors is chrysin (flavone), while stilbenes seem to be the most effective CYP1B1 inhibitors. In most cases, their effect is not specific. Therefore, different approaches are made to find the best candidate for the drug prototype of a new therapeutic or chemopreventive agent and to improve its pharmacokinetic parameters. This review presents and discusses the possible effects on major CYPs involved in estrogen metabolism by phytochemicals from the most investigated classes, namely flavonoids, stilbenes, and glucosinolates breakdown products. Full article

Chirality plays a key role in the effectiveness and toxicity of bioactive compounds. Usnic acid (UA), a lichen metabolite, exists as two enantiomers. Despite numerous studies on its biological properties, enantioselective aspects remain poorly recognized. This study assessed the cytotoxicity of UA enantiomers against colon, prostate, thyroid, brain, and breast cancer cell lines, as well as non-cancerous cells. Cell viability was determined by the MTT assay after 24, 48, and 72 h. Colon cancer HCT116 cells were the most sensitive (IC₅₀ ~10 µg/mL, 72 h), with no enantiomeric dominance. In prostate cancer PC3 cells, (+)-UA was more effective. Moderate cytotoxic effect was noted for thyroid cancer cells; however, this was evaluated for the first time. MDA-MB-231 breast cancer cells were strongly affected (IC₅₀ 15.8 and 20.2 µg/mL for (+)- and (−)-UA, 72 h), as compared to MCF7 cells. Brain cancer cells were the least affected, as so were normal astrocytes. UA had no effect on normal colon epithelial cells but showed moderate toxicity in prostate, thyroid, and breast cells. To conclude, the overall cytotoxicity of (+)-UA was stronger than its (−)-enantiomer, while the latter compound was more toxic to normal cells. These findings highlight the advantage of (+)-UA, especially in chemopreventive strategies. Full article

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease linked to fibrosis and hepatocellular carcinoma (HCC). Gut-derived lipopolysaccharide (LPS) promotes hepatic inflammation, fibrosis, and angiogenesis through toll-like receptor 4 (TLR4) signaling. This study examined the effects of rifaximin, a non-absorbable, gut-targeted antibiotic, on MASH-related liver fibrosis and early hepatocarcinogenesis, with a focus on the LPS–epiregulin–IL-8–angiogenesis axis.MASH was induced in Fischer 344 rats using a choline-deficient, L-amino acid-defined high-fat diet (CDAHFD). Rifaximin (30 mg/kg/day) was orally administered for 12 weeks. Liver histology, gene expression, intestinal permeability, LPS levels, and angiogenic markers were evaluated. Rifaximin reduced hepatic inflammation, fibrosis, hydroxyproline content, and fibrogenic gene expression. The number and size of GST-P-positive preneoplastic lesions and proliferation-related genes were decreased. Portal LPS levels and Kupffer cell activation declined, with downregulation of Lbp, Cd14, Tlr4, and inflammatory cytokines. Rifaximin decreased hepatic epiregulin and IL-8 expression, attenuated CD34-positive neovascularization, and suppressed proangiogenic gene expression, accompanied by improved intestinal barrier function and reduced gut permeability. Rifaximin mitigates MASH progression by restoring gut barrier integrity, limiting LPS translocation, and inhibiting fibrogenic and angiogenic pathways. These results suggest its potential as a chemopreventive agent in MASH-related hepatocarcinogenesis. Full article

Background/Objectives: Natural products are important in healthcare due to their accessibility and linkage to a healthy lifestyle. However, their effectiveness is uncertain due to insufficient scientific data. Cancer patients are frequent users of natural products to relieve symptoms or for chemoprevention. Eugenia uniflora leaf essential oil (EO), traditionally used for digestive disorders, emerges as a potential antineoplastic agent. We investigated the cytotoxic and antiproliferative effects of E. uniflora EO in human normal CCD 841 CoN and tumoral Caco-2 colonic cell lines. Methods: CCD 841 CoN and Caco-2 cells were exposed to different concentrations of E. uniflora EO, and the cytotoxicity was determined by MTT and Trypan Blue assays. Cell proliferation kinetics were analyzed at a low EO concentration, and the induction of DNA damage and oxidative stress was assessed by Comet and Cellular ROS assays. Results: Both cell lines exhibited cytotoxicity produced by the EO and decreased cell viability of the exposed cells and their progeny. CCD 841 CoN proliferation was impaired by low EO concentration, while the proliferation kinetics of the Caco-2 cells was modified. EO treatment induced variable DNA damage and oxidative stress depending on the cell line. Conclusions: Our results suggest that E. uniflora EO may prevent the proliferation of normal cells, inducing loss of viability. The EO produced cytotoxic and antiproliferative effects in tumoral cells by inducing DNA damage and increased oxidative stress. These effects support the consideration of E. uniflora EO (or its bioactive compounds) as a potential agent for the chemoprevention and treatment of colorectal cancer. Full article

Caffeine, one of the most widely consumed bioactive compounds worldwide, is gaining recognition for its potential anticancer properties beyond its well-known neurological and metabolic effects. Mechanistically, caffeine exerts anti-tumor activity by modulating key cellular pathways involved in carcinogenesis, including the inhibition of phosphodiesterases, antagonism of adenosine A2A receptors, and disruption of the DNA damage response through ATR-Chk1 pathway inhibition. These actions collectively promote apoptosis, suppress tumor cell proliferation, and impair metastatic spread. In vitro and in vivo studies have demonstrated that caffeine can enhance the cytotoxic effects of chemotherapeutic agents and radiation therapy, suggesting a synergistic role in conventional cancer treatments. Epidemiological data further supports an inverse association between habitual caffeine consumption and the incidence of several cancers, notably liver, colorectal, breast, and prostate cancers. Among these, the most consistent experimental and clinical evidence exists for liver and colorectal cancer, where caffeine’s modulatory effects on inflammation and cell proliferation have been repeatedly observed. Additionally, caffeine’s anti-oxidant and anti-inflammatory properties may contribute to a microenvironment less conducive to tumor initiation and progression. While promising, the anticancer effects of caffeine are influenced by factors such as dosage, individual genetic variability, and cancer type, underscoring the need for further clinical investigation. This review explores the emerging role of caffeine as a potential chemopreventive and adjuvant therapeutic agent in oncology. Full article

Bioactive peptides from black soldier fly larvae (BSFL) protein hydrolysates have gained attention for their health-promoting properties. Our previous study demonstrated the chemopreventive potential of BSFL hydrolysates prepared with Alcalase (ASBP-AH) in colon cancer cells; their in vivo efficacy has not been fully elucidated. This study evaluated the chemopreventive effects of ASBP-AH, processed by spray-drying (ASBP-AHS) or freeze-drying (ASBP-AHF), in a diethylnitrosamine (DEN) and 1,2-dimethylhydrazine (DMH)-induced rat model of early-stage colorectal carcinogenesis. Oral administration of ASBP-AHS or ASBP-AHF significantly reduced aberrant crypt foci (ACF) and downregulated PCNA, COX-2, and NF-κB expression, without affecting apoptosis. Furthermore, both treatments restored microbial species richness and shifted gut microbial diversity disrupted by carcinogen exposure. ASBP-AHS specifically enriched short-chain fatty acid (SCFA)-producing bacteria, while ASBP-AHF favored anti-inflammatory microbial signatures. Likewise, correlation analysis revealed positive associations between microbial changes and SCFA levels, particularly with ASBP-AHS. Peptidomic profiling identified identical peptides in both hydrolysates, including stable pyroglutamyl-containing sequences with potential anti-inflammatory and microbiota-modulating effects. These findings support the in vivo chemopreventive potential of ASBP-AH and its promise as a functional food ingredient for promoting gut health and reducing colorectal cancer risk. Full article

Chitosan is increasingly utilized in combination with melatonin in novel formulations for a wide range of therapeutic applications. As a biocompatible and biodegradable polymer, chitosan exhibits notable properties, including antioxidant, antimicrobial, moisturizing, and absorption capabilities, in addition to a high potential for chemical modification due to its functional groups. These characteristics make it a valuable material in biomedical, pharmaceutical, cosmetic, food packaging, and environmental applications. Melatonin, an indoleamine primarily synthesized in the pineal gland but also found in various peripheral organs and in diverse organisms—including plants, bacteria, and fungi—has been extensively investigated for its antioxidant, anti-apoptotic, and anti-inflammatory activities, as well as its roles in immunomodulation, mitochondrial function, and melanin biosynthesis. This review summarizes recent advances in the combined use of chitosan and melatonin, with emphasis on their synergistic effects in wound healing, anti-cancer therapies, tissue engineering (i.e., skin and bone regeneration), and drug delivery systems. Additional potential applications are discussed in the context of cosmetology, aesthetic medicine, and veterinary practice. Full article

Docetaxel is extensively used for treating different types of cancer; however, its clinical efficacy is primarily limited by myelotoxicity and peripheral neuropathy, adverse effects that often lead to treatment discontinuation. This study aimed to establish a preclinical model in Wistar rats for the simultaneous induction of myelotoxicity and peripheral neuropathy associated with docetaxel administration, enabling the evaluation of potential chemopreventive agents. Four distinct docetaxel administration schemes were assessed by performing behavioral nociceptive tests and complete blood cell counts. After establishing the damage model (5 mg/kg/week docetaxel for six weeks), we co-administered 100 mg/kg/week oral dimethyl fumarate to assess its protective effect. Dimethyl fumarate attenuated docetaxel-induced hyperalgesia, likely through preserving normal nerve fiber density in sciatic nerves, but neutropenia was not significantly mitigated. An alternative regimen with additional pre-administered doses of dimethyl fumarate showed a trend toward neutropenia attenuation and suggested an interesting inhibition of docetaxel-induced rat vibrissae loss. Chou-Talalay isobolographic analyses on prostate cancer cell lines revealed that dimethyl fumarate does not impair the therapeutic effect of docetaxel at most combination ratios evaluated; rather, synergistic effects were observed. This experimental model proved useful and will facilitate further research into the protective role of dimethyl fumarate and other potential chemoprotective agents. Full article

In this study, the chemopreventive effects of rosmarinic acid (RA), a major phenolic acid of the plant Rosmarinus officinalis L., against the carcinogenic naturally occurring mycotoxin aflatoxin B1 (AFB1) were investigated using both in silico and in vitro approaches. The in silico investigation of the chemical reactions between rosmarinic acid and the carcinogenic metabolite of AFB1, aflatoxin B1 exo-8,9-epoxide (AFBO), was conducted by activation free energies calculations with DFT functionals M11-L and MN12-L, in conjunction with the 6-311++G(d,p) flexible basis set and implicit solvation model density (SMD), according to a newly developed quantum mechanics-based protocol for the evaluation of carcinogen scavenging activity (QM-CSA). Following the computational analyses, the chemoprotective effects of RA were further studied in vitro in human hepatocellular carcinoma HepG2 cells by analyzing its influence on AFB1-induced genotoxicity using a comet assay, γH2AX, and p-H3, while its impact on cell proliferation and cell cycle modulation was assessed using flow cytometry. Our computational results revealed that the activation free energy required for the reaction of RA with AFBO (14.86 kcal/mol) is significantly lower than the activation free energy for the competing reaction of AFBO with guanine (16.88 kcal/mol), which indicates that RA acts as an efficient natural scavenger of AFBO, potentially preventing AFB1-specific DNA adduct formation. The chemoprotective activity of RA was confirmed through in vitro experiments, which demonstrated a statistically significant (p < 0.05) reduction in AFB1-induced single- and double-strand breaks in HepG2 cells exposed to a mixture of AFB1 and RA at non-cytotoxic concentrations. In addition, RA reversed the AFB1-induced reduction in cell proliferation. Full article

Background/Objectives: Prostate cancer (PCa) is the second most common malignancy among men worldwide and a leading cause of cancer-related mortality. In 2022, over 1.4 million new cases were reported globally, with a prevalence exceeding 5 million. Despite its widespread occurrence, the incidence and mortality of PCa show substantial geographic variation, influenced by factors such as genetic predisposition, healthcare access, lifestyle, and the adoption of screening programs. Regions with high PCa incidence, such as Northern America and Oceania, often have lower mortality rates due to early detection and advanced healthcare infrastructure. Conversely, areas with limited access to medical resources, such as parts of Africa and Latin America, experience higher mortality rates. Methods: This review explores non-modifiable risk factors such as age, family history, and race, emphasizing their role in PCa development and progression. Results: Modifiable factors, including diet, physical activity, alcohol consumption, and smoking, are also addressed, with evidence suggesting their potential in mitigating risk. Emerging data on medications such as 5-alpha reductase inhibitors and statins, as well as dietary supplements such as vitamins D, indicate their potential for chemoprevention, though further research is needed to solidify these findings. Healthcare disparities, especially in low- and middle-income regions, highlight the need for equitable access to diagnostic tools and treatment options. The review underscores the significance of tailored screening approaches, particularly in high-risk populations, to optimize outcomes while minimizing overdiagnosis and overtreatment. Conclusions: The review concludes with recommendations for future research, including the need for standardized screening protocols and the exploration of novel biomarkers for early detection. By synthesizing epidemiological data and current evidence, this review aims to enhance understanding of PCa risk factors, geographic disparities, and preventive strategies, ultimately contributing to improved global PCa management and outcomes. Full article

Postbiotics, defined as a preparation of inanimate microorganisms and/or their components, including metabolic byproducts, have gained recognition as promising modulators of gut health and disease, offering advantages over probiotics in terms of safety, stability, and formulation. This systematic review investigates the therapeutic potential of postbiotics derived from functional foods in the context of colorectal cancer (CRC), a leading cause of cancer-related mortality worldwide. Despite encouraging preclinical findings, translation into clinical practice remains limited due to a paucity of robust human trials, revealing a significant gap and the need for further translational research. Key bioactive categories of postbiotics are described, alongside their anti-inflammatory, immunomodulatory, and chemopreventive mechanisms. Through comprehensive literature mapping, this review uniquely categorizes research according to the experimental models employed, i.e., in vitro, in silico, in vivo, and ex vivo, and advanced models such as organoids and organ-on-chip platforms. The latter offers greater physiological relevance by closely mimicking human tissue architecture and microenvironment. These models help demonstrate how postbiotics may influence tumorigenesis through mechanisms involving inflammation, apoptosis, epigenetic regulation, and the maintenance of gut barrier integrity. Finally, the review summarizes recent innovations in their delivery strategies and calls for comprehensive mechanistic studies and high-quality clinical trials to validate postbiotics as safe and effective adjuncts in CRC prevention, therapy, and management. Full article

Phytosterols, essential components of plant cell membranes, are abundant in fruits, vegetables, nuts, and seeds. Among them, β-sitosterol, campesterol, and stigmasterol have drawn significant interest for their well-documented biological activities. This review highlights recent advancements in extraction and analytical methods aimed at improving phytosterol yield, maintaining chemical stability, and reducing environmental impact. These innovative, eco-friendly techniques offer promising alternatives to traditional extraction approaches and hold potential for industrial-scale use. Phytosterols possess various bioactive properties, including antioxidant, anti-inflammatory, chemopreventive, cholesterol-lowering, and neuroprotective effects. Through these mechanisms, dietary phytosterols may help prevent cardiovascular and neurodegenerative diseases, type 2 diabetes, and certain cancers. Recent studies have focused on the identification, isolation, purification, and characterization of phytosterols from diverse food matrices, along with assessing their health benefits. However, the specific molecular pathways responsible for their pharmacological actions remain poorly understood, highlighting the need for further research, particularly in human clinical trials. This review provides a comprehensive overview of the extraction strategies, biological functions, and mechanisms of action of phytosterols, offering valuable insights for developing phytosterol-enriched functional foods and nutraceuticals. Full article

The Fabaceae family is known for the presence of isoflavones—phytoestrogens with potential chemopreventive effects against hormone-dependent cancers. This study aimed to optimize isoflavones extraction using a fractional factorial design and to quantitatively and qualitatively analyze 32 Fabaceae species native to Polish flora by HPLC-UV-VIS to indicate new, rich plant sources of isoflavones. The optimal extraction method was a 60 min reflux with 50% methanol and a plant material-to-solvent ratio of 1:125. The highest isoflavone levels were found in Trifolium medium (26.70 mg/g d.m.), Genista tinctoria (19.65 mg/g d.m.), and Trifolium pratense (12.56 mg/g d.m.). The obtained extracts were further evaluated for cytotoxic and antiproliferative activity against MCF7 and MDA-MB-231 human breast cancer cells. Genista tinctoria showed the highest cytotoxicity against MCF7, while Cytisus scoparius and Ononis arvensis were most effective against MDA-MB-231 at a dose of 500 µg/mL. The extracts were also characterized by varied, potent antioxidant properties, important in chemoprevention. A strong correlation was observed between isoflavone content and cytotoxic and antiproliferative activity exclusively in the estrogen receptor-positive MCF7 cell line. Importantly, the tested extracts demonstrated no toxic effects on normal human liver (HepG2), thyroid (Nthy-ori 3-1), or breast (MCF10A) cells, indicating a favorable safety profile. Full article