Toxin Research Articles

Biosensors for Seafood Safety Control—A Review

The increased demand for consuming seafood has made seafood production undergo a rapid period of growth. However, seafood has a high risk of contamination from harmful microorganisms and marine toxins which can cause health problems for humans consuming it. Concerning this issue, monitoring seafood safety has become a center of attention for researchers, and developing effective methods for detecting contamination in seafood has become a critical research field. In this context, biosensors have served as a promising approach to monitor seafood contamination. Compared to conventional methods, biosensors have some key benefits such as high sensitivity, selectivity, portability, and user-friendly operation. Along with significant advances in biosensors, processes of seafood monitoring can be simplified and performed outside the laboratory. In this review article, we describe the mechanisms of two main types of biosensors regarding electrochemical and optical biosensors. The current reports within the last five years on the application of these biosensors for seafood monitoring are also summarized.

Dual‐Active Centers Linked by Oxygen Transfer for Enhancing Proximity‐Orientation Effect of Nanozyme

AbstractProximity‐orientation effects (POE) are essential for enzymes, as the spatial arrangement and orientation of catalytic sites strongly influence substrate binding and enhance catalysis. However, nanozymes often face limitations due to weak POE arising from uniform catalytic interfaces. Herein, Co atoms are incorporated into the lattice of Pt‐based nanozymes, exploiting differences in electron configuration and atomic radius between transition metals and noble metals. This integration induced lattice distortion formed new catalytic sites, and restricted the transport path, thereby enhancing the POE. Such transition metal‐doped alloy nanozyme (TANzyme) can be functioned as a self‐cascading nanozyme with artificial catalase‐oxidase activity. Density functional theory calculations demonstrated that the Pt site selectively decomposed H2O2 into H2O and O2, while the Co site specifically adsorbed O2 and conversed into superoxide anions, so an oxygen transfer path to connect dual‐active centers not only increased the POE but also improved catalytic specificity. Additionally, by leveraging the efficient catalytic property of TANzyme, a visual origami‐based sensing strategy is developed for the cascade detection of H2O2, nucleic acids, and marine toxins. This strategy highlighted the pivotal role of POE in enhancing the catalytic specificity of nanozymes, mimicking natural POE in enzymes, and providing a solution to design next‐generation nanozymes.

Bioaccumulation of environmental pollutants and marine toxins in bivalve molluscs: a review

Seafood is both nutritionally and economically significant, with bivalve molluscs being particularly valuable for monitoring environmental pollutants due to their filter-feeding nature and ability to bioaccumulate pollutants. While not often linked to food poisoning, these molluscs can occasionally introduce health risks, highlighting the need for vigilant monitoring. This review provides a thorough analysis of pollutants—including persistent and emerging pollutants, as well as marine toxins—found in bivalve molluscs between 2019 and 2024. Among the studied pollutants, plasticizers and alkaloids are the most frequently analyzed, with liquid and gas chromatography (GC) tandem mass spectrometry (MS) the predominant methods, although novel approaches to determine these compounds, such as sensors, have also emerged in recent years. However, many studies are focused on establishing pollutant content without addressing bioaccumulation (BA) factors, and a lack of standardization in species and sampling locations complicates comparisons between the different published works. Despite some studies linking human activity and algal blooms to BA dynamics, more comprehensive research is needed. Additionally, limited data on the depuration capacity of molluscs underscores the need for further investigation. Although pollutant levels generally remain within legal limits, many substances remain unregulated. Environmental factors also play a critical role in influencing BA, emphasizing the need for future studies to focus on BA factors to better understand these complex dynamics.

Stabilizing Scaffold for Short Peptides Based on Knottins.

Bombesin (BBN) is a short peptide with a high affinity for receptors that are expressed on the surface of various types of cancer cells. However, a full length BBN molecule has low in vivo stability. In our study, we propose the use of peptide toxins, derived from animal and plant toxins, as scaffold molecules to enhance the bioavailability and stability of bombesin. These peptides possess a unique structure known as an inhibitory cystine knot. We synthesized structures in which short bombesin was incorporated into various domains of arthropod and plant toxins using solid-phase peptide synthesis. The stability under different conditions was assessed through high-performance liquid chromatography, and binding to cell cultures expressing the bombesin receptor was analyzed. Additionally, toxicity to cell cultures was evaluated using fluorescence microscopy. The data obtained demonstrated that placing the short peptide between the first and second cysteine residues in arachnid toxins results in increased in vitro stability and bioavailability, as well as low cytotoxicity. Arachnid toxins with an inhibitory cystine knot can be considered as a scaffold for increasing the stability of therapeutic peptides.

Insecticidal activities of three recombinant venom proteins of the predatory stink bug, Arma custos.

Widespread resistance of insect pests to insecticides and transgenic crops in the field is a significant challenge for sustainable agriculture, and calls for the development of novel alternative strategies to control insect pests. One potential resource for the discovery of novel insecticidal molecules is natural toxins, particularly those derived from the venoms of insect predators. In this study, we identified three insecticidal proteinaceous toxins from the venom glands (VGs) of the predatory stink bug, Arma custos (Hemiptera: Asopinae). Transcriptomic analysis of A. custos VGs revealed 151 potentially secreted VG-rich venom proteins. Three VG-rich venom proteins (designated AcVP1 ~ 3) were produced by overexpression in Escherichia coli. Injection of the recombinant proteins into tobacco cutworm (Spodoptera litura) larvae showed that all of the three recombinant proteins caused paralysis, liquefaction and death. Injection of recombinant proteins into rice brown planthopper (Nilaparvata lugens) nymphs showed higher insecticidal activities, among which a trypsin (AcVP2) caused 100% mortality postinjection at 1.27 pmol mg-1 body weight. A natural toolkit for the discovery of insecticidal toxins from predatory insects has been revealed by the present study. © 2024 Society of Chemical Industry.

Exposure assessment of the European adult population to deoxynivalenol – Results from the HBM4EU Aligned Studies

Mycotoxins are natural toxins produced by fungi that may cause adverse health effects thus constituting a public health concern. Deoxynivalenol (DON), a mycotoxin affecting the immune system and causing intestinal disorders, was selected as a priority under the European Human Biomonitoring Initiative (HBM4EU). Urinary total DON levels (tDON) of 1270 participants from six countries were used to characterize the internal exposure of the adult European population and identify the most relevant determinants of exposure. tDON concentrations’ P50 and P95 were in the range of 0.41–10.16 µg/L (0.39–9.05 µg/g crt) and 3.25–46.58 µg/L (2.12–33.50 µg/g crt) respectively. Higher tDON levels were observed for (i) male participants from France and Germany, (ii) samples collected in spring and summer, (iii) participants with a lower educational level, (iv) participants living in rural areas, (v) individuals without a job in France and Luxembourg, while in Portugal higher exposure was observed in working individuals, (vi) individuals with higher consumption of cereals and bread. The proportion of individuals with exposure levels exceeding the HBM-GV of 23 µg/L was 12.3 %, ranging from 0.8 % to 20.7 % in the individual countries. This study on mycotoxins exposure has used post harmonized questionnaire data and validated analytical methodologies for analysis and covered countries representing the four geographical regions of Europe, having produced much needed knowledge on the exposure of the European adult population to deoxynivalenol.

USE OF APITOXIN AS AN INTERVENTION IN THE TREATMENT OF DERMATOLOGICAL INFLAMMATIONS

Bee venom (BV), produced by the species Apis mellifera, is one of the most recognized and widely studied natural toxins, with increasing use in integrative medicine. This venom contains a variety of chemical substances, including peptides such as melittin, apamin, adolapin and the MCD peptide, as well as enzymes such as phospholipase A2 (PLA2), hyaluronidase, acid phosphomonoesterase and lysophospholipase. Amines, such as histamine, dopamine and norepinephrine, are also present, which contribute to its antimicrobial, anti-inflammatory, immunomodulatory and anticancer properties. Studies suggest that it has promising pharmacological effects, especially in the treatment of inflammation. OBJECTIVE: This study aims to investigate the therapeutic effects of bee venom in the treatment of dermatological inflammation, exploring its potential as a natural alternative with proven anti-inflammatory properties. METHODOLOGY: A systematic review of the literature was carried out, focusing on primary articles and results of randomized clinical trials (RCTs) conducted in vivo and in vitro, published between 2014 and 2024. RESULTS: In models with induced atopic dermatitis (AD) such as mice, phospholipase A2 (PLA2), a compound derived from BV, was shown to significantly reduce skin thickness and inflammatory cytokine levels, both in animal models and humans, highlighting the importance of confirming its clinical applicability. Therefore, therapies may include everything from topical application of BV to the use of emollients and cosmetics with these compounds, based on their pharmacological properties. CONCLUSION: This review highlighted the potential of bee venom as a promising alternative in the treatment of dermatological inflammations, due to its anti-inflammatory and immunomodulatory properties. Studies in animal models and in vitro suggest that compounds such as melittin and phospholipase A2 (PLA2) inhibit inflammatory mediators and alleviate symptoms of atopic dermatitis and acne. In addition, research indicates that VB can block inflammatory signaling pathways, such as NF-κB and MAPK, reinforcing its therapeutic potential in the management of skin inflammation, especially in topical applications.

High-resolution mass spectrometry-based suspect and nontarget screening of natural toxins in foodstuffs and risk assessment of dietary exposure

Daily dietary intake inevitably exposes individuals to various natural toxins, which may pose potential health threats. Focusing only on specific toxins could underestimate dietary risks. Therefore, we have developed a suspect and nontarget method based on ultrahigh-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) to screen both known and unknown natural toxins in various foodstuffs. An in-house database containing 2952 natural toxins including fungal toxins, phytotoxins, animal toxins and cyanotoxins was established, facilitating suspect screening. Predicted retention time and mass spectrometry data were employed to enhance the confidence levels. Subsequently, Nontarget screening method was conducted based on molecular network analysis, annotating the edges and nodes through modified types and fragmentation characteristics. Finally, we analyzed 102 foodstuff samples and identified a total of 90 natural toxins, including mycotoxins and phytotoxins, with 65 identified by suspect screening and 25 by nontarget screening. Based on measured concentrations, the daily per capita dietary intake of total natural toxins was estimated, it was below risk doses for natural toxins with available reference values. Overall, this work established a novel method for the comprehensive identification of natural toxins in foodstuffs and emphasized the importance of dietary risk assessment for natural toxins.

Evaluating the stability of tropane and opium alkaloids during baking in homemade gluten-free poppy seed crackers

Nowadays, alternative flour to wheat, such as teff and corn are increasingly used in gluten-free bakery products, and seeds, such as poppy seeds (whole or ground) are added for their beneficial nutritional properties. However, these ingredients may be contaminated with natural toxins such as tropane (TAs) and opium (OAs) alkaloids. To reduce toxin exposure, it is essential to assess their thermal degradation during baking. The study aimed to quantify TAs and OAs in doughs before and after baking to evaluate their degradation while preparing homemade gluten-free ground poppy seed crackers. To achieve this, a novel methodology involving solid-liquid extraction (SLE) and solid-phase extraction (SPE) with a bifunctionalized mesostructured silica SBA-15 sorbent (50 mg), followed by UHPLC-MS/MS analysis, was developed and validated. The method validation showed good linearity (R2 ≥ 0.991), precision (%RSD ≤17%), accuracy (88–104% for TAs and 79–106% for OAs), and low quantification limits (0.6–1.1 μg/kg for TAs and 0.06–0.46 mg/kg for OAs). The results showed no significant reduction of the alkaloids in the homemade gluten-free ground poppy seed crackers, showing that both families of natural toxins can remain in foods even after intense heat treatments, highlighting the need for accurate monitoring of these natural toxins in processed food.

An Optimized Method for the Simultaneous Analysis of 16 Lipophilic Marine Toxins Using LC–MS/MS with Solid-Phase Extraction Cleanup in Seafood Matrices

An Optimized Method for the Simultaneous Analysis of 16 Lipophilic Marine Toxins Using LC–MS/MS with Solid-Phase Extraction Cleanup in Seafood Matrices

Streamlined Flow Synthesis of Plasmonic Nanoparticles and SERS Detection of Uremic Toxins with Trace-Level Liquid Volumes in a Microchamber.

Rapid detection of uremic toxins is crucial due to their severe health risks, including oxidative stress, inflammation, neurotoxicity, cardiovascular complications, and progression of chronic kidney disease. Surface-enhanced Raman spectroscopy (SERS) may provide sensitive, fast, and clinical-grade real-time monitoring of these toxins, enabling effective management with timely dialysis treatments. This study introduces a 3D-printed microchamber that integrates the fabrication of plasmonic metal nanoparticles for the in-flow detection of biological toxins and pharmaceutical drugs using SERS, making it ideal for on-site diagnostics in clinical settings. The microchamber supports quantitative and highly reproducible detection with liquid volumes under 100 μL, which is crucial for trace-level biomarker detection and minimizing cross-contamination. It employs a tunable solvent exchange method for the in situ synthesis of silver nanoparticles (AgNPs) on flexible PDMS or rigid Si wafer substrates, avoiding costly nanofabrication techniques. Ultralow detection limits were achieved for two model compounds and three pharmaceutical drugs: 10-11 M for rhodamine 6G, 10-7 M for adenine, and 10-6 M for the pharmaceutical drugs. A total of 13 biological toxins, including three neurotransmitters, one neuromodulator, five amino acids, two polyamines, and two urea cycle metabolites, were detected with quantitative limits ranging from 10-3 to 10-6 M, all below permissible levels and aligning with physiological conditions. SERS detection within microchambers facilitates rapid on-site analysis, proving ideal for personalized health monitoring, point-of-care diagnostics, and environmental pollution assessment.

Microfluidic Optical Aptasensor for Small Molecules Based on Analyte-Tuned Growth of Gold Nanoseeds and Machine Learning-Enhanced Spectrum Analysis: Rapid Detection of Mycotoxins.

Natural toxins, mainly small molecules, are a category of chemical hazards in agri-food systems that pose threats to both public health and food security. Current standard methods for monitoring these toxins, predominantly based on liquid chromatography-mass spectrometry, are costly, labor-intensive, and complex. This study presents the development of a novel microfluidic optical aptasensor for rapid detection of small molecules based on analyte-tuned growth of gold nanoseeds combined with machine learning-enhanced spectrum analysis. We discovered and optimized a previously unreported growth pattern of aptamer-coated nanoparticles in the presence of different concentrations of analyte, enabling the detection of a major mycotoxin in food. The entire analysis was miniaturized on a customized microfluidic platform, allowing for automated spectral acquisition with precise liquid manipulation. A machine learning model, based on random forest with feature engineering, was developed and evaluated for spectrum analysis, significantly enhancing the prediction of mycotoxin concentrations. This approach extended the detection limit determined by the conventional method (∼72 ppb with high variation) to a wider range of 10 ppb to 100 ppm with high accuracy (overall mean absolute percentage error of 5.7%). The developed analytical tool provides a promising solution for detecting small molecules and monitoring chemical hazards in agri-food systems and the environment.

Design of a Duplex-to-Complex Structure-Switching Approach for the Homogeneous Determination of Marine Biotoxins in Water.

In this report, we describe a fluorescent assay for the detection of six marine toxins in water. The mechanism of detection is based on a duplex-to-complex structure-switching approach. The six aptamers specific to the targeted cyanotoxins were conjugated to a fluorescent dye, carboxyfluorescein (FAM). In parallel, complementary DNA (cDNA) sequences specific to each aptamer were conjugated to a fluorescence quencher BHQ1. In the absence of the target, an aptamer-cDNA duplex structure is formed, and the fluorescence is quenched. By adding the toxin, the aptamer tends to bind to its target and releases the cDNA. The fluorescence intensity is consequently restored after the formation of the complex aptamer-toxin, where the fluorescence recovery is directly correlated with the analyte concentration. Based on this principle, a highly sensitive detection of the six marine toxins was achieved, with the limits of detection of 0.15, 0.06, 0.075, 0.027, 0.041, and 0.026 nM for microcystin-LR, anatoxin-α, saxitoxin, cylindrospermopsin, okadaic acid, and brevetoxin, respectively. Moreover, each aptameric assay showed a very good selectivity towards the other five marine toxins. Finally, the developed technique was applied for the detection of the six toxins in spiked water samples with excellent recoveries.

In vitro hepatic 3D cell models and their application in genetic toxicology: a systematic review

The rapid development of new chemicals and consumer products has raised concerns about their potential genotoxic effects on human health, including DNA damage leading to serious diseases. For such new chemicals and pharmaceutical products, international regulations require genotoxicity data, initially obtained through in vitro tests, followed by in vivo experiments, if needed. Traditionally, laboratory animals have been used for this purpose, however, they are costly, ethically problematic, and often unreliable due to species differences. Therefore, innovative more accurate in vitro testing approaches are rapidly being developed to replace, refine and reduce (3R) the use of animals for experimental purposes and to improve the relevance for humans in toxicology studies. One of such innovative approaches are in vitro three-dimensional (3D) cell models, which are already being highlighted as superior alternatives to the two-dimensional (2D) cell cultures that are traditionally used as in vitro models for the safety testing of chemicals and pharmaceuticals. 3D cell models provide physiologically relevant information and more predictive data for in vivo conditions. In the review article, we provide a comprehensive overview of 3D hepatic cell models, including HepG2, HepG2/C3A, HepaRG, human primary hepatocytes, and iPSC-derived hepatocytes, and their application in the field of genotoxicology. Through a detailed literature analysis, we identified 31 studies conducted between 2007 and April 2024 that used a variety of standard methods, such as the comet assay, the micronucleus assay, and the γH2AX assay, as well as new methodological approaches, including toxicogenomics, to assess the cytotoxic and genotoxic activity of chemicals, nanoparticles and natural toxins. Based on our search, we can conclude that the use of in vitro 3D cell models for genotoxicity testing has been increasing over the years and that 3D cell models have an even greater potential for future implementation and further refinement in genetic toxicology and risk assessment.

7Method for Detection of Naturally Occurring Toxins in Human Urine Using Liquid Chromatography High Resolution Mass Spectrometry.

Natural toxins present an ongoing risk for human exposure that requires a rapid, accurate diagnosis for proper response. In this study, a qualitative liquid chromatography high resolution mass spectrometry (LC-HRMS) method was developed and validated for the detection of a large, diverse selection of natural toxins. Data-dependent acquisition was performed to identify compounds with an in-house mass spectral library of 129 hazardous toxins that originate from plants, animals, and fungi. All 129 compounds were spiked into human urine, extracted, and evaluated for spectral library matching. Of these, 92 toxins met the quality criteria and underwent validation in urine matrix based on American National Standards Institute (ANSI) guidelines. A generalized workflow for method expansion was developed and enables the rapid addition of relevant compounds to the established method. This LC-HRMS method achieves efficient detection of natural toxins in urine, and the created workflow can rapidly increase compound coverage via method expansion.

Reports of tropane alkaloid poisonings and analytical techniques for their determination in food crops and products from 2013 to 2023.

Food safety is crucial to attaining food security and sustainability. Unsafe foods for human and animal consumption lead to product recalls and rejection, negatively impacting the global economy and trade. Similarly, climate change can adversely affect the availability of safe and nutritious food at the table. The changing climatic conditions and global food trade and transport can make the movement of toxic plants possible, resulting in food crops being increasingly invaded by some species of plants that produce toxic secondary metabolites, such as tropane alkaloids (TAs).Datura stramoniumfrom the Solanaceae plant family is an invasive and virulent plant that produces high amounts of two TAs, atropine and scopolamine. Various food poisoning events following accidental or deliberate ingestion of foods contaminated by atropine and scopolamine from seeds ofD. stramoniumhave been recorded in different locations globally. Due to these incidents, regulatory agencies require the development of plant toxin detection methods that can be used in the food chain as early as possible. This systematic review thus focuses on the TA determination techniques in food and feeds published between 2013 and 2023. A particular focus was given to the sample preparation methods, the improvements of each technique claimed, and data to support the performance of each method, especially the ability to measure at or below the maximum level. The review concludes with other technological advancements, including rapid spectroscopy, electrophoresis, and colorimetric methods, as well as the possibility of coupling with smartphones for use in on-farm detection and the challenges in applying them.

Synthesis of the Spirocyclic Imine Fragment of Portimines Using a γ-Hydroxymethyl-α,β-butenolide Dienophile in a Diastereoselective Diels-Alder Reaction.

The synthesis of the spirocyclic imine fragment of the portimine family of marine toxins has been achieved. A densely functionalized key lactone-ester intermediate was assembled via a highly diastereoselective Diels-Alder cycloaddition, involving a novel γ-hydroxymethyl-α,β-butenolide dienophile. A Stille coupling was employed to install the vinyl group. Selective elaboration of the two carbonyl groups successfully afforded the spirocyclic imine fragment.

Characterising okadaic acid (OA) toxicity both in vitro and in vivo, using a comparative porcine model (MOKAPIG).

Food toxicology helps to protect the health and safety of consumers by a better understanding of the impact of xenobiotics and natural toxins on public health. Professors Mauro Dacasto (UNIPD), Flavia Girolami (UNITU), and Anna Zaghini (UNIBO) have collaborated on a research assessing the impact of aflatoxin B1 (a harmful mycotoxin) on bovine and human health. In their current project, MOKAPIG, the researchers are using comparative human and pig in vitro models as well as the weaned pig as an animal model to shed a light on the fate of differing levels of okadaic acid (OA) in target tissues such as the gastrointestinal tract and the liver. The goal of the two-year project is to expand the existing knowledge on the effects of OA on humans and pigs, including data on OA toxicokinetics, toxicodynamics and mechanistic toxicology. This will help to improve the protection of consumer health and seafood safety. MOKAPIG will first assess OA cytotoxicity and its bioavailability in vitro, characterise and profile OA metabolism and carry out comparative toxicogenomic studies. Then, the project will explore the in vivo toxicity of OA using a porcine animal model. The reasoning behind selecting a porcine over a rodent model is that mice show limitations for the assessment of marine toxins comparative toxicity, e.g, species-differences in xenobiotic metabolism.

Specific anti-toxic immunotherapy: use in medical practice and perspectives

The results of use of approaches and means of antitoxic immunotherapy in medical practice are summarized: passive transfer of various variants of antibodies specific to toxic compounds, vaccination – specific active immunization with vaccines carrying determinants of the immunochemical specificity of target toxic compounds. The practical effectiveness of the known approaches of passive transfer and vaccination is associated with the ability of specific antibodies, by binding target bioactive compounds with pronounced toxicity, to change the availability of corresponding structures in the body-targets and, in the presence of a sufficient number of specific antibodies with high binding ability to the target compounds, neutralize their toxicity. In medical practice, polyspecific heterologous antisera or the gamma globulin fraction of antisera (extremely rare monoclonal antibodies of narrow specificity) are widely used for passive transfer as antidotes in the treatment of victims in order to prevent deaths and extensive necrosis of soft tissues at the site of the bite of poisonous snakes and insects. Active immunization – vaccination with appropriate antigenic drugs should create in immunized individuals a state of humoral immunity with the corresponding characteristics of antibody formation specific to the target compound. When a target toxic compound enters an immunized organism, it is also possible to neutralize its toxicity. The most successful experience in using the principles of active immunization as a technology for specific antitoxic therapy is associated with the practice of using toxoids for toxinemic infections. Specific practical techniques used to achieve the effectiveness of possible approaches to specific antitoxic immunotherapy in the form of passive transfer of specific antibodies or their fragments are considered: to combat lethal infections in the pathogenesis of which the toxic effects of bacterial exotoxins are significant; when treating victims of snake and insect bites, exposure to poisons of marine organisms, algae and plant toxins; in the treatment of severe intoxication with certain low molecular weight toxic substances: digoxin, colchicine, tricyclic antidepressants. The most successful experiences of using the principles of active immunization as a technology for specific antitoxic therapy, based on the use of toxoids with specificity for diphtheria, tetanus, botulism, cholera, typhoid fever, dysentery, gas gangrene and other toxinemic infections, are also considered. The fairly high immunogenicity of toxoids with the possibility of activating both constitutional and adaptive immunity has become the basis for their use as macromolecular carriers of hapten analogues of narcotic substances – a promising direction in drug addiction, in the implementation of which a number of experimental molecular and combined vaccines of opiates, methamphetamine, cocaine, and nicotine. This variant of practical efforts in medicine can be regarded as a new direction of specific antitoxic immunotherapy – an option to combat drug addiction by vaccinating drug addicts.

Green Poison : A Sustainable Approach to Use Plant Toxin as an Anticancer Agent

The rising interest in plant-derived phytochemicals as cancer therapies has revealed numerous bio-active compounds with potent therapeutic potential. Compounds like vinca alkaloids, taxane , and berberine exhibit diverse biological activities, including anti-tumor, proving effective against various cancer types. Despite the toxicity of some medicinal plants, this feature can be harnessed for drug discovery, offering new treatments for cancer. Plant metabolites target tumor growth by inhibiting tumor-promoting enzymes, repairing DNA, and boosting immune responses. Compounds like vinblastine disrupt micro-tubule dynamics, while curcumin inhibits cancer cell proliferation. Toxic plant-derived metabolites, such as podophyllotoxin and camptothecin, demonstrate unique cancer-fighting mechanisms by targeting topoisomerases and inducing apoptosis. Integrating these phytochemical promise for advancing cancer prevention and treatment, offering more sustainable and effective options.