UniDL4BioPep: a universal deep learning architecture for binary classification in peptide bioactivity.

Identification of potent peptides through model prediction can reduce benchwork in wet experiments. However, the conventional process of model buildings can be complex and time consuming due to challenges such as peptide representation, feature selection, model selection and hyperparameter tuning. Recently, advanced pretrained deep learning-based language models (LMs) have been released for protein sequence embedding and applied to structure and function prediction. Based on these developments, we have developed UniDL4BioPep, a universal deep-learning model architecture for transfer learning in bioactive peptide binary classification modeling. It can directly assist users in training a high-performance deep-learning model with a fixed architecture and achieve cutting-edge performance to meet the demands in efficiently novel bioactive peptide discovery. To the best of our best knowledge, this is the first time that a pretrained biological language model is utilized for peptide embeddings and successfully predicts peptide bioactivities through large-scale evaluations of those peptide embeddings. The model was also validated through uniform manifold approximation and projection analysis. By combining the LM with a convolutional neural network, UniDL4BioPep achieved greater performances than the respective state-of-the-art models for 15 out of 20 different bioactivity dataset prediction tasks. The accuracy, Mathews correlation coefficient and area under the curve were 0.7-7, 1.23-26.7 and 0.3-25.6% higher, respectively. A user-friendly web server of UniDL4BioPep for the tested bioactivities is established and freely accessible at https://nepc2pvmzy.us-east-1.awsapprunner.com. The source codes, datasets and templates of UniDL4BioPep for other bioactivity fitting and prediction tasks are available at https://github.com/dzjxzyd/UniDL4BioPep.

Integrated annotation prioritizes metabolites with bioactivity in inflammatory bowel disease.

Microbial biochemistry is central to the pathophysiology of inflammatory bowel diseases (IBD). Improved knowledge of microbial metabolites and their immunomodulatory roles is thus necessary for diagnosis and management. Here, we systematically analyzed the chemical, ecological, and epidemiological properties of ~82k metabolic features in 546 Integrative Human Microbiome Project (iHMP/HMP2) metabolomes, using a newly developed methodology for bioactive compound prioritization from microbial communities. This suggested >1000 metabolic features as potentially bioactive in IBD and associated ~43% of prevalent, unannotated features with at least one well-characterized metabolite, thereby providing initial information for further characterization of a significant portion of the fecal metabolome. Prioritized features included known IBD-linked chemical families such as bile acids and short-chain fatty acids, and less-explored bilirubin, polyamine, and vitamin derivatives, and other microbial products. One of these, nicotinamide riboside, reduced colitis scores in DSS-treated mice. The method, MACARRoN, is generalizable with the potential to improve microbial community characterization and provide therapeutic candidates.

The protective effect and bioactive compounds of Astragalus membranaceus against neurodegenerative disorders via alleviating oxidative stress in Drosophila.

Oxidative stress is proposed as a regulatory element in various neurological disorders, which is involved in the progress of several neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Antioxidant drugs are widely used to alleviate neurodegenerative disorders. Astragalus membranaceus (Huangqi, AM) is a commonly used medicinal herb with a wide range of pharmacological effects. Here, the protective effect and mechanism of AM extract (AME) and its bioactive compounds against neurodegenerative disorders via alleviating oxidative stress were detected using adult Drosophila melanogaster. The drug safety was measured by development analysis; oxidative stress resistance ability was detected by survival rate under H2O2 environment; ROS level was detected by DHE staining and gstD1-GFP fluoresence assay; antioxidative abilitiy was represent by measuring antioxidant enzyme activity, antioxidative-related gene expression, and ATP and MFN2 levels. The neuroprotective effect was evaluated by lifespan and locomotion analysis in Aß42 transgenic and Pink1B9 mutants. AME dramatically increased the survival rates, improved the CAT activity, restored the decreased mRNA expressions of Sod1, Cat, and CncC under H2O2 stimulation, and ameliorated the neurobehavioral defects of the AD and PD. Thirteen small molecules in AM had antioxidant function, in which vanillic acid and daidzein had the most potent antioxidant effect. Vanillic acid and daidzein could increase the activities of SOD and CAT, GSH level, and the expressions of antioxidant genes. Vanillic acid could improve the levels of ATP and MFN2, and mRNA expressions of ND42 and SDHC to rescue mitochondrial dysfunction. Furthermore, vanillic acid ameliorated neurobehavioral defects of PD. Daidzein ameliorated neurobehavioral defect of Aß-induced AD mode. Taken together, AM plays a protective role in oxidative damage, thereby as a potential natural drug to treat neurodegenerative disorders.

Targeting anoikis resistance as a strategy for cancer therapy.

Anoikis, known as matrix detachment-induced apoptosis or detachment-induced cell death, is crucial for tissue development and homeostasis. Cancer cells develop means to evade anoikis, e.g. anoikis resistance, thereby allowing for cells to survive under anchorage-independent conditions. Uncovering the mechanisms of anoikis resistance will provide details about cancer metastasis, and potential strategies against cancer cell dissemination and metastasis. Here, we summarize the principal elements and core molecular mechanisms of anoikis and anoikis resistance. We discuss the latest progress of how anoikis and anoikis resistance are regulated in cancers. Furthermore, we summarize emerging data on selective compounds and nanomedicines, explaining how inhibiting anoikis resistance can serve as a meaningful treatment modality against cancers. Finally, we discuss the key limitations of this therapeutic paradigm and possible strategies to overcome them. In this review, we suggest that pharmacological modulation of anoikis and anoikis resistance by bioactive compounds could surmount anoikis resistance, highlighting a promising therapeutic regimen that could be used to overcome anoikis resistance in cancers.

Prospects of earthworm coelomic fluid as a potential therapeutic agent to treat cancer.

Cancer is a major public health concern because it is one of the main causes of morbidity and mortality worldwide. As a result, numerous studies have reported the development of new therapeutic compounds with the aim of selectively treating cancer while having little negative influence on healthy cells. In this context, earthworm coelomic fluid has been acknowledged as a rich source of several bioactive substances that may exhibit promising anticancer activity. Therefore, the objective of the present review is to evaluate the findings of the reported studies exploring the antitumor effects of coelomic fluid in the context of its possible utilization as a natural therapeutic agent to cure different types of cancer. The possible mechanisms underlying the coelomic fluid's anticancerous potential as well as the possibility for future development of cutting-edge therapeutic agents utilizing coelomic fluid-derived natural bioactive compounds to treat cancer disorders have been discussed along with future challenges. In addition, the feasibility of encapsulation of bioactive compounds derived from coelomic fluid with nanomaterials that could be further explored to attain more effective anticancer competence is discussed.

Marine Bioactive Peptides: Anti-Photoaging Mechanisms and Potential Skin Protective Effects.

Skin photoaging, resulting from prolonged exposure to ultraviolet radiation, is a form of exogenous aging that not only impacts the aesthetic aspect of the skin but also exhibits a strong correlation with the onset of skin cancer. Nonetheless, the safety profile of non-natural anti-photoaging medications and the underlying physiological alterations during the process of photoaging remain inadequately elucidated. Consequently, there exists a pressing necessity to devise more secure interventions involving anti-photoaging drugs. Multiple studies have demonstrated the noteworthy significance of marine biomolecules in addressing safety concerns related to anti-photoaging and safeguarding the skin. Notably, bioactive peptides have gained considerable attention in anti-photoaging research due to their capacity to mitigate the physiological alterations associated with photoaging, including oxidative stress; inflammatory response; the abnormal expression of matrix metalloproteinase, hyaluronidase, and elastase; and excessive melanin synthesis. This review provides a systematic description of the research progress on the anti-photoaging and skin protection mechanism of marine bioactive peptides. The focus is on the utilization of marine bioactive peptides as anti-photoaging agents, aiming to offer theoretical references for the development of novel anti-photoaging drugs and methodologies. Additionally, the future prospects of anti-aging drugs are discussed, providing an initial reference for further research in this field.

Actinomycetes Associated with Arthropods as a Source of New Bioactive Compounds.

Antimicrobial resistance is one of the main global threats to human health in the 21st century due to the rapid appearance of bacterial resistance and the lack of novel bioactive compounds. Natural products, especially from Actinomycetes, remain the best source to refill the drug industry pipeline. Different strategies have been pursued to increase the chances of discovering new molecules, such as studying underexplored environments like arthropod symbionts, which represent a relevant reservoir for active metabolites. This review summarizes recent research on the identification of bioactive molecules produced by Actinomycetes associated with arthropods' microbiome. The metabolites have been categorized based on their structural properties and host, highlighting that multidisciplinary approaches will be the key to fully understanding this complex relationship.

A Review of Bioactive Compound Effects from Primary Legume Protein Sources in Human and Animal Health.

The global demand for sustainable and nutritious food sources has catalyzed interest in legumes, known for their rich repertoire of health-promoting compounds. This review delves into the diverse array of bioactive peptides, protein subunits, isoflavones, antinutritional factors, and saponins found in the primary legume protein sources-soybeans, peas, chickpeas, and mung beans. The current state of research on these compounds is critically evaluated, with an emphasis on the potential health benefits, ranging from antioxidant and anticancer properties to the management of chronic diseases such as diabetes and hypertension. The extensively studied soybean is highlighted and the relatively unexplored potential of other legumes is also included, pointing to a significant, underutilized resource for developing health-enhancing foods. The review advocates for future interdisciplinary research to further unravel the mechanisms of action of these bioactive compounds and to explore their synergistic effects. The ultimate goal is to leverage the full spectrum of benefits offered by legumes, not only to advance human health but also to contribute to the sustainability of food systems. By providing a comprehensive overview of the nutraceutical potential of legumes, this manuscript sets a foundation for future investigations aimed at optimizing the use of legumes in the global pursuit of health and nutritional security.

Exploring the Therapeutic Potential: Bioactive Molecules and Dietary Interventions in Multiple Sclerosis Management.

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system, the etiology of which is still unclear. Its hallmarks are inflammation and axonal damage. As a disease primarily impacting younger individuals, the social cost of MS is high. It has been proposed that environmental factors, smoking, and dietary habits acting on a genetic susceptibility play a role in MS. Recent studies indicate that diet can significantly influence the onset and progression of MS. This review delves into the impact of natural bioactive molecules on MS development and explores the dietary interventions that hold promise in managing the disease. Dietary patterns, including ketogenic and Mediterranean diets, are discussed. Theories about the potential mechanistic associations beneath the noted effects are also proposed. Several dietary components and patterns demonstrated the potential for a significant impact on MS. However, extensive prospective clinical trials are necessary to fully understand the role of natural bioactive molecules as disease modifiers in MS.

Sickle Cell Disease: Current Drug Treatments and Functional Foods with Therapeutic Potential.

Sickle cell anemia (SCA), the most common form of sickle cell disease (SCD), is a genetic blood disorder. Red blood cells break down prematurely, causing anemia and often blocking blood vessels, leading to chronic pain, organ damage, and increased infection risk. SCD arises from a single-nucleotide mutation in the ß-globin gene, substituting glutamic acid with valine in the ß-globin chain. This review examines treatments evaluated through randomized controlled trials for managing SCD, analyzes the potential of functional foods (dietary components with health benefits) as a complementary strategy, and explores the use of bioactive compounds as functional food ingredients. While randomized trials show promise for certain drugs, functional foods enriched with bioactive compounds also hold therapeutic potential. Further research is needed to confirm clinical efficacy, optimal dosages, and specific effects of these compounds on SCD, potentially offering a cost-effective and accessible approach to managing the disease.

Self-Assembled Nanocarrier Delivery Systems for Bioactive Compounds.

Although bioactive compounds (BCs) have many important functions, their applications are greatly limited due to their own defects. The development of nanocarriers (NCs) technology has gradually overcome the defects of BCs. NCs are equally important as BCs to some extent. Self-assembly (SA) methods to build NCs have many advantages than chemical methods, and SA has significant impact on the structure and function of NCs. However, the relationship among SA mechanism, structure, and function has not been given enough attention. Therefore, from the perspective of bottom-up building mechanism, the concept of SA-structure-function of NCs is emphasized to promote the development of SA-based NCs. First, the conditions and forces for occurring SA are introduced, and then the SA basis and molecular mechanism of protein, polysaccharide, and lipid are summarized. Then, varieties of the structures formed based on SA are introduced in detail. Finally, facing the defects of BCs and how to be well solved by NCs are also elaborated. This review attempts to describe the great significance of constructing artificial NCs to deliver BCs from the aspects of SA-structure-function, so as to promote the development of SA-based NCs and the wide application of BCs.

Chemo-Enzymatic Derivatization of Glycerol-Based Oligomers: Structural Elucidation and Potential Applications.

Switching from oil-based to bio-based feedstocks to ensure the green transition to a sustainable and circular future is one of the most pressing challenges faced by many industries worldwide. For the cosmetics and personal and house care industries there is a strong drive to accelerate this transition from the customers that starts favoring the purchase of naturally derived and bio-degradable products over the traditionally available products. In this work we developed a series of fully biobased macromolecules constituted of a glycerol-based oligoester backbone. Based on the subsequent derivatization with fatty acids or peptides, the resulting products may find application as emulsifiers, wetting agents, and potential vectors for the delivery of bioactive peptides. All steps of the resulting macromolecules were conducted following the green chemistry principles with no toxic or environmentally damaging compounds that were used in the overall production process.

Identification of DPP-IV inhibitory peptides derived from buffalo colostrum: Mining through bioinformatics, in silico and in vitro approaches.

Bioactive peptides derived from foods provide physiological health benefits beyond nutrition. This study focused on profiling small peptide inhibitors against two key serine proteases, dipeptidyl peptidase-IV (DPP-IV) and prolyl oligopeptidase (POP). DPP-IV is a well-known protein involved in diverse pathways regulating inflammation, renal, cardiovascular physiology, and glucose homeostasis. POP is yet another key target protein for neurodegenerative disorders. The study evaluated peptide libraries of buffalo colostrum whey and fat globule membrane proteins derived from pepsin and pepsin-pancreatin digestion through in silico web tools and structure-based analysis by molecular docking and binding free-energy estimation, followed by in vitro assay for DPP-IV inhibition for the lead peptides. The bioinformatic study indicated 49 peptides presented motifs with DPP-IV inhibition while 5 peptides with sequences for POP inhibition. In the molecular docking interactions study, 22 peptides interacted with active site residues of DPP-IV and 3 peptides with that of POP. The synthesized peptides, SFVSEVPEL and LTFQHNF inhibited DPP-IV in vitro with an IC50 of 193.5 µM and 1.782 mM, respectively. The study revealed the key residues for inhibition of DPP-IV and POP thus affirming the DPP-IV inhibitory potential of milk-derived peptides.

Integrative transcriptome and metabolome analysis reveals the discrepancy in the accumulation of active ingredients between Lycium barbarum cultivars.

MAIN CONCLUSION: The combined analysis of transcriptome and metabolome provided molecular insight into the dynamics of multiple active ingredients biosynthesis and accumulation across different cultivars of Lycium barbarum. Lycium barbarum L. has a high concentration of active ingredients and is well known in traditional Chinese herbal medicine for its therapeutic properties. However, there are many Lycium barbarum cultivars, and the content of active components varies, resulting in inconsistent quality between Lycium barbarum cultivars. At present, few research has been conducted to reveal the difference in active ingredient content among different cultivars of Lycium barbarum at the molecular level. Therefore, the transcriptome of 'Ningqi No.1' and 'Qixin No.1' during the three development stages (G, T, and M) was constructed in this study. A total of 797,570,278 clean reads were obtained. Between the two types of wolfberries, a total of 469, 2394, and 1531 differentially expressed genes (DEGs) were obtained in the 'G1 vs. G10,' 'T1 vs. T10,' and 'M1 vs. M10,' respectively, and were annotated with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) orthology identifiers. Using these transcriptome data, most DEGs related to the metabolism of the active ingredients in 'Ningqi No.1' and 'Qixin No.1' were identified. Moreover, a widely targeted metabolome analysis of the metabolites of 'Ningqi 1' and 'Qixin 1' fruits at the maturity stage revealed 1,135 differentially expressed metabolites (DEMs) in 'M1 vs. M10,' and many DEMs were associated with active ingredients such as flavonoids, alkaloids, terpenoids, and so on. We further quantified the flavonoid, lignin, and carotenoid contents of the two Lycium barbarum cultivars during the three developmental stages. The present outcome provided molecular insight into the dynamics of multiple active ingredients biosynthesis and accumulation across different cultivars of Lycium barbarum, which would provide the basic data for the formation of Lycium barbarum fruit quality and the breeding of outstanding strains.

Identifying multi-functional bioactive peptide functions using multi-label deep learning.

The bioactive peptide has wide functions, such as lowering blood glucose levels and reducing inflammation. Meanwhile, computational methods such as machine learning are becoming more and more important for peptide functions prediction. Most of the previous studies concentrate on the single-functional bioactive peptides prediction. However, the number of multi-functional peptides is on the increase; therefore, novel computational methods are needed. In this study, we develop a method MLBP (Multi-Label deep learning approach for determining the multi-functionalities of Bioactive Peptides), which can predict multiple functions including anti-cancer, anti-diabetic, anti-hypertensive, anti-inflammatory and anti-microbial simultaneously. MLBP model takes the peptide sequence vector as input to replace the biological and physiochemical features used in other peptides predictors. Using the embedding layer, the dense continuous feature vector is learnt from the sequence vector. Then, we extract convolution features from the feature vector through the convolutional neural network layer and combine with the bidirectional gated recurrent unit layer to improve the prediction performance. The 5-fold cross-validation experiments are conducted on the training dataset, and the results show that Accuracy and Absolute true are 0.695 and 0.685, respectively. On the test dataset, Accuracy and Absolute true of MLBP are 0.709 and 0.697, with 5.0 and 4.7% higher than those of the suboptimum method, respectively. The results indicate MLBP has superior prediction performance on the multi-functional peptides identification. MLBP is available at https://github.com/xialab-ahu/MLBP and http://bioinfo.ahu.edu.cn/MLBP/.

Development of a virus-based affinity ultrafiltration method for screening virus-surface-protein-targeted compounds from complex matrixes: Herbal medicines as a case study.

Herbal medicines (HMs) are one of the main sources for the development of lead antiviral compounds. However, due to the complex composition of HMs, the screening of active compounds within these is inefficient and requires a significant time investment. We report a novel and efficient virus-based screening method for antiviral active compounds in HMs. This method involves the centrifugal ultrafiltration of viruses, known as the virus-based affinity ultrafiltration method (VAUM). This method is suitable to identify virus specific active compounds from complex matrices such as HMs. The effectiveness of the VAUM was evaluated using influenza A virus (IAV) H1N1. Using this method, four compounds that bind to the surface protein of H1N1 were identified from dried fruits of Terminalia chebula (TC). Through competitive inhibition assays, the influenza surface protein, neuraminidase (NA), was identified as the target protein of these four TC-derived compounds. Three compounds were identified by high performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometry (LC/MS), and their anti-H1N1 activities were verified by examining the cytopathic effect (CPE) and by performing a virus yield reduction assay. Further mechanistic studies demonstrated that these three compounds directly bind to NA and inhibit its activity. In summary, we describe here a VAUM that we designed, one that can be used to accurately screen antiviral active compounds in HMs and also help improve the efficiency of screening antiviral drugs found in natural products.

Advances in separation and identification of biologically important milk proteins and peptides.

Milk is a rich source of biologically important proteins and peptides. In addition, milk contains a variety of extracellular vesicles (EVs), including exosomes, that carry their own proteome cargo. EVs are essential for cell-cell communication and modulation of biological processes. They act as nature carriers of bioactive proteins/peptides in targeted delivery during various physiological and pathological conditions. Identification of the proteins and protein-derived peptides in milk and EVs and recognition of their biological activities and functions had a tremendous impact on food industry, medicine research, and clinical applications. Advanced separation methods, mass spectrometry (MS)-based proteomic approaches and innovative biostatistical procedures allowed for characterization of milk protein isoforms, genetic/splice variants, posttranslational modifications and their key roles, and contributed to novel discoveries. This review article discusses recently published developments in separation and identification of bioactive proteins/peptides from milk and milk EVs, including MS-based proteomic approaches.

Metabolomics approach for phenolic compounds profiling of soursop (Annona muricata L.) fruit during postharvest storage.

INTRODUCTION: Soursop (Annona muricata L.) is a crop with medicinal properties and numerous bioactive compounds. Ripening is a complex process that regulates fruit quality and changes in metabolite content, such as flavonoids, polyphenols, and organic acids. OBJECTIVES: This study aimed to analyze the phenolic profiling of soursop fruit ripening. METHODS: The metabolic changes in different days of storage of soursop fruits were investigated using a semi-metabolomic approach based on ultra-performance liquid chromatography coupled to electrospray ionization quadrupole-time of flight mass spectrometry (UPLC-ESI-QTOF-MS). Further, multivariate analysis such as supervised partial least squares discriminant analysis (PLS-DA) was conducted to identify differential metabolites. RESULTS: A total of 68 metabolites were identified in soursop fruit during postharvest storage. A higher number of metabolites were identified in the Day zero (D0) compared to the Day one (D1), Day three (D3), and Day five (D5), belonging to flavonoids, other polyphenols, phenolic acids, and organic acids. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the pathways of flavone and flavonol biosynthesis, flavonoid biosynthesis, and biosynthesis of secondary metabolites were mostly enriched. Additionally, we included all the compounds and their postharvest storage in the public Phenolics profile database. CONCLUSIONS: Here, we show that the stage of ripening has a significant effect on the phenolic content, highlighting the point of cut (D0) and the onset of senescence (D5). The findings of this study provide new insights into the soursop fruit quality and may contribute to the identification of metabolic markers for its storage.

Green synthesized silver nanoparticles from Phoenix dactylifera synergistically interact with bioactive extract of Punica granatum against bacterial virulence and biofilm development.

The global rise of antibiotic resistance poses a substantial risk to mankind, underscoring the necessity for alternative antimicrobial options. Developing novel drugs has become challenging in matching the pace at which microbial resistance is evolving. Recently, nanotechnology, coupled with natural compounds, has emerged as a promising solution to combat multidrug-resistant bacteria. In the present study, silver nanoparticles were green-synthesized using aqueous extract of Phoenix dactylifera (variety Ajwa) fruits and characterized by UV-vis spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM) coupled with Energy dispersive X-ray analysis (EDX), Transmission electron microscopy (TEM) and Thermogravimetric-differential thermal analysis (TGA-DTA). The in-vitro synergy of green synthesized P. dactylifera silver nanoparticle (PD-AgNPs) with selected antibiotics and bioactive extract of Punica granatum, i.e., ethyl acetate fraction (PGEF), was investigated using checkerboard assays. The most effective synergistic combination was evaluated against the QS-regulated virulence factors production and biofilm of Pseudomonas aeruginosa PAO1 by spectroscopic assays and electron microscopy. In-vivo anti-infective efficacy was examined in Caenorhabditis elegans N2 worms. PD-AgNPs were characterized as spherical in shape with an average diameter of 28.9 nm. FTIR analysis revealed the presence of functional groups responsible for the decrease and stabilization of PD-AgNPs. The signals produced by TGA-DTA analysis indicated the generation of thermally stable and pure crystallite AgNPs. Key phytocompounds detected in bioactive fractions include gulonic acid, dihydrocaffeic acid 3-O-glucuronide, and various fatty acids. The MIC of PD-AgNPs and PGEF ranged from 32 to 128 µg/mL and 250-500 µg/mL, respectively, against test bacterial strains. In-vitro, PD-AgNPs showed additive interaction with selected antibiotics (FICI 0.625-0.75) and synergy with PGEF (FICI 0.25-0.375). This combination inhibited virulence factors by up to 75 % and biofilm formation by 84.87 % in P. aeruginosa PAO1. Infected C. elegans worms with P. aeruginosa PAO1 had a 92.55 % survival rate when treated with PD-AgNPs and PGEF. The combination also reduced the reactive oxygen species (ROS) level in C. elegans N2 compared to the untreated control. Overall, these findings highlight that biosynthesized PD-AgNPs and bioactive P. granatum extract may be used as a potential therapeutic formulation against MDR bacteria.

It comes from the sea: macroalgae-derived bioactive compounds with anti-cancer potential.

Nature derived compounds represent a valuable source of bioactive molecules with enormous potential. The sea is one of the richest environments, full of skilled organisms, where algae stand out due to their unique characteristics. Marine macroalgae adapt their phenotypic characteristics, such as chemical composition, depending on the environmental conditions where they live. The compounds produced by these organisms show tremendous potential to be used in the biomedical field, due to their antioxidant, anti-inflammatory, immunomodulatory, and anti-cancer properties.Cancer is one of the deadliest diseases in the world, and the lack of effective treatments highlights the urgent need for the development of new therapeutic strategies. This review provides an overview of the current advances regarding the anti-cancer activity of the three major groups of marine macroalgae, i.e., red algae (Rhodophyta), brown algae (Phaeophyceae), and green algae (Chlorophyta) on pancreatic, lung, breast, cervical, colorectal, liver, and gastric cancers as well as leukemia and melanoma. In addition, future perspectives, and limitations regarding this field of work are also discussed.