Search Results (431)

Background/Objectives: Natural products have long been regarded as a cornerstone in the discovery and development of novel therapeutic agents. Accumulating evidence indicates that natural products represent promising pharmacological candidates for cancer treatment. This review provides a holistic overview of novel identified natural products as a continuing source of bioactive compounds, with particular emphasis on recent advances and their applications in anticancer therapy over the past five years. Methods: A literature search was conducted using PubMed, Scopus, and Web of Science to identify relevant studies published within the past five years. Predefined keywords and Boolean operators (e.g., “natural products”, “anticancer”, “drug discovery”, “secondary metabolites”, “signaling pathways”, “epigenetics”) were applied, with search strategies adapted to each database. Eligible studies included original research articles and reviews reporting on newly identified natural products with anticancer activity, with emphasis on chemical diversity, biological effects, and molecular mechanisms of action. Additional references were identified through manual screening of bibliographies. The selected literature was evaluated using a qualitative, interpretative approach consistent with narrative review methodology, and findings were critically synthesized and thematically organized. Results: Growing evidence indicates that multiple newly identified natural products target mitochondrial metabolism and interact with alternative tubulin binding sites, thereby highlighting their potential as anticancer agents. In addition, emerging compounds have been shown to affect DNA integrity and transcriptional regulation, while also acting as systems-level modulators of key oncogenic signaling pathways, including PI3K/Akt, NF-κB, and MAPK. Recent studies further demonstrate that natural products can modulate multiple layers of epigenetic regulation, including DNA methylation, histone acetylation, histone methylation, and non-coding RNA networks. Conclusions: Current evidence supports the concept that natural products primarily function as multi-target biological modulators rather than classical single-target inhibitors in cancer biology. A persistent challenge remains the translational gap between preclinical efficacy and clinical application, as the majority of naturally derived candidate compounds remain confined to in vitro or early in vivo validation. Future progress will therefore depend on systematically aligning the multi-target pharmacology of natural products with defined cancer vulnerabilities and clinically actionable therapeutic strategies. Full article

The body’s microbiota plays a fundamental role in maintaining homeostasis and influences immune function, metabolism, and tissue integrity. A growing body of research suggests that fluctuations in the composition and abundance of individual microbiota populations may influence cancer development and the effectiveness of therapy. The condition of microbiota dysbiosis has been demonstrated to induce chronic inflammation, immune system dysregulation, and, most significantly, modulation of molecular pathways that promote tumorigenesis. The efficacy and toxicity of cancer treatment can be influenced by the composition of the microbiota. Bacteria can modify the effectiveness and toxicity of chemotherapy and immunotherapy by affecting drug metabolism and the body’s immune response. In contrast, the development of anticancer therapies that utilize bacteria is gaining increasing interest. This alternative to conventional treatment utilizes the natural ability of certain bacterial species to selectively colonize hypoxic and necrotic environments. The exploration of natural and genetically modified bacteria as vectors for the delivery of cytotoxins, immunomodulators, or therapeutic genes in the combat of cancer is a current area of research. In addition, their capacity to stimulate an antitumor immune response is also exploited. Preclinical investigations in animals have demonstrated the efficacy of this therapeutic approach, underscoring the promise of bacterial therapies as either an adjunct to conventional treatment or as a standalone strategy for combating cancer. This article synthesizes the current knowledge regarding the role of microbiota in carcinogenesis in animals and discusses recent developments in the field of bacterial therapies. The text also addresses the challenges, safety considerations, and future perspectives associated with translating microbiota-targeted and bacterial therapies into veterinary and comparative oncology. Full article

Hypoxia is one of the most important factors limiting the effectiveness of modern anticancer therapies, particularly photodynamic therapy (PDT). The hypoxia of the tumor microenvironment results from abnormal angiogenesis and the high metabolic demand of cancer cells, which leads to reduced oxygen availability necessary for generating reactive oxygen species (ROS). Consequently, conventional therapeutic approaches, mainly based on the type II PDT mechanism, show limited effectiveness under hypoxic conditions. In response to these limitations, strategies are being developed to increase oxygen availability within the tumor. Of particular importance are nanocarriers based on perfluorocarbons (PFCs), which, due to their high gas solubility, can effectively transport and release oxygen in the tumor microenvironment. Research indicates that the use of such systems leads to improved PDT efficiency by increasing the production of singlet oxygen and enhancing cancer cell damage. Parallelly, alternative approaches independent of high oxygen concentration, including type I photosensitizers, are being developed. Unlike classical type II mechanisms, they generate free radicals through electron transfer reactions, which allows effective action even under conditions of significant hypoxia. This approach significantly expands the possibilities of using PDT in the treatment of tumors with low oxygen levels. Current research directions focus on integrating various therapeutic strategies to achieve a synergistic effect. Hybrid systems combining oxygen delivery (e.g., using PFCs) with the use of type I photosensitizers and other treatment methods, such as chemotherapy or immunotherapy, show the greatest clinical potential. Such multifunctional approaches simultaneously allow improving tumor oxygenation and increasing the efficiency of ROS generation, which makes them a promising strategy for the future of anticancer therapies. Full article

Triple-negative breast cancer (TNBC) is a clinically aggressive malignancy with extremely limited effective targeted therapies. Natural products are promising alternatives for anticancer drug discovery, whereas integrated computational approaches serve as efficient tools for novel lead identification. Herein, four novel spiro-polycyclic sesquiterpene [4+2] trimers (Inubritantrimers A–D) and eight synthetic derivatives from Inula britannica L. were investigated via DFT calculations at the ωB97xD/6-311++G(2d,p) level (for geometric, electronic, spectral, and reactivity parameters), network pharmacology, molecular docking against seven core breast cancer-related targets, 500 ns all-atom molecular dynamics (MD) simulation, and MM/PBSA analysis. The results showed that the endo-type cycloaddition products had superior structural stability, with all reactions thermodynamically spontaneous (ΔG < 0). Compound 11 exhibited the most potent and balanced binding activity, with a docking free energy of −13.45 kcal/mol to MTOR; MD and MM/PBSA confirmed stable complex formation (total binding free energy −21.13 kcal/mol), driven predominantly by hydrophobic interactions. This study first established a comprehensive stereochemistry–electronic structure–property–activity relationship for this rare sesquiterpene trimer class and identified compound 11 as a promising MTOR-targeted TNBC lead. It provided a theoretical basis for developing high-efficiency, low-toxicity natural anticancer agents. Full article

Silver nanoparticles (AgNPs) have attracted substantial scientific interest in biomedical research owing to their unique physicochemical characteristics, broad-spectrum antimicrobial activity, plasmonic properties, and therapeutic versatility. Although conventional physicochemical synthesis methods enable controlled NPs fabrication, their dependence on hazardous reagents, elevated energy input, and environmentally detrimental processing conditions has stimulated the development of sustainable biogenic alternatives. Biological synthesis utilizing plants, microorganisms, fungi, algae, and purified biomolecules has emerged as an eco-friendly and bio-compatible strategy for AgNP fabrication, enabling simultaneous reduction, stabilization, and intrinsic biofunctionalization of NPs. However, traditional biogenic synthesis remains constrained by limited mechanistic understanding, poor batch reproducibility, inadequate control over physicochemical properties, and challenges in large-scale manufacturing. Recent advances in bioengineering have transformed this field through the integration of metabolic engineering, synthetic biology, microfluidic-assisted synthesis, artificial intelligence-guided process optimization, and continuous-flow biomanufacturing, collectively enabling precision fabrication of biogenic AgNPs with enhanced uniformity, scalability, and functional tunability. Furthermore, strategic surface engineering and functionalization have expanded the applicability of biogenic AgNPs across targeted anticancer therapy, antimicrobial intervention, wound healing, regenerative medicine, drug delivery, and theranostic imaging. Despite these advancements, critical challenges remain regarding nano–bio interactions, toxicological safety, regulatory compliance, and translational scalability. Unlike conventional reviews focused primarily on green synthesis approaches, this review critically highlights emerging bioengineering paradigms that enable programmable, scalable, and precision-controlled biogenic AgNP fabrication. This review comprehensively examines next-generation paradigms and strategies for AgNPs biosynthesis, elucidates the molecular mechanisms governing their formation, highlights emerging functionalization and biomedical application paradigms, and discusses current translational barriers. Forming biogenic composites of AgNPs and heteroatom doped carbon nanodots needs intense research in near future. Full article

The development of biocompatible functional nanostructures has emerged as a key driver in advancing nanomedicine, environmental remediation, and sustainable energy technologies. However, conventional synthesis methods often rely on toxic reagents, hazardous solvents, and energy-intensive processes, raising significant concerns regarding environmental impact and biological safety. In this context, green synthesis has gained increasing attention as a sustainable alternative, utilizing biological systems, renewable resources, and environmentally benign solvents to produce functional nanomaterials. This mini-review provides an overview of recent advances in the green synthesis of organic, inorganic, and hybrid nanostructures, highlighting their physicochemical properties and functional performance. Particular emphasis is placed on their applications in nanomedicine, including drug delivery, bioimaging, antimicrobial and anticancer therapies, and theranostic platforms. Additionally, their roles in environmental applications, such as pollutant degradation and water treatment, and in energy-related systems, including catalysis, solar energy conversion, and energy storage, are discussed with selected representative examples. Despite significant progress, key challenges remain, including limited mechanistic understanding, reproducibility issues, scalability constraints, and uncertainties related to long-term toxicity and environmental impact. Addressing these limitations will be essential for the safe and large-scale implementation of green nanotechnology. Overall, the integration of green chemistry principles with advanced nanomaterial design offers a promising pathway toward the development of multifunctional, sustainable, and high-performance nanostructures capable of addressing global health, environmental, and energy challenges. Full article

The current literature indicates that type 2 diabetes (T2DM) significantly increases the risk of cancer, including pancreatic cancer (PC). While metformin’s primary role is the management of T2DM, its utility extends to systemic anti-cancer effects against various cancers. Nevertheless, its impact appears limited to risk reduction, as its efficacy as a primary or adjuvant treatment for established cancer remains unproven in clinical settings. This meta-analysis aimed to evaluate the association between metformin use—both as monotherapy and in combination with other antidiabetic drugs (ADs)—and the risk of PC. We synthesized data from 16 observational studies identified through PubMed, Cochrane Library, and Clinical Trials using the Population, Intervention, Comparison, Outcomes, and Study Type (PICOT) framework. The data were analyzed using Cochrane Review Manager software 5.4, with results reported as the relative risk (RR) and 95% confidence interval (95% CI) for each comparative group; statistical significance was defined as p-value < 0.05. Our findings indicate that metformin demonstrated a significant reduction in overall PC risk when compared to the pooled group of alternative ADs. Furthermore, metformin significantly lowers PC risk compared to sulfonylureas (SUs), alpha-glucosidase inhibitors (AGIs), and insulin. Conversely, metformin use was associated with a markedly elevated PC risk relative to thiazolidinediones (TZDs) and DPP-4 inhibitors (DPP4i). Considering metformin monotherapy vs. its combination with other ADs, we found that metformin lowered the risk of PC compared to its combination with SUs and AGIs but elevated the PC risk relative to its combination with TZDs and DPP4i. To conclude, these results suggest that metformin may protect patients with T2DM from PC development. However, individual PC risk and diabetes compliance should be taken into account when deciding whether to add an additional AD(s) to metformin therapy. Full article

Introduction: Heat shock proteins (HSPs) are stress-responsive molecular chaperones that are frequently dysregulated in cancer and contribute to tumorigenesis, invasion, metastasis, immune interactions, and resistance to therapy. Distinct HSP families, including HSP27, HSP60, HSP70, HSP90, and HSP110, promote malignant progression through complementary effects on apoptosis regulation, mitochondrial function, proteostasis, and stabilization of oncogenic signaling pathways. This makes HSPs attractive therapeutic targets. Their coordinated roles within stress-adaptive chaperone networks further garner interest in targeting multiple HSP families in cancer therapy. Discussion: Preclinical and clinical studies have established multiple HSP families as promising anticancer targets; however, clinical translation of HSP-directed therapies has been challenged by toxicity, compensatory heat shock responses, and resistance mechanisms. Many N-terminal HSP90 inhibitors have shown clinical utility but have also highlighted the need for alternative approaches, including C-terminal inhibition, HSP70-directed therapies, and rational combination strategies targeting compensatory survival pathways. Emerging inhibitors targeting HSP27, HSP60, and HSP110, as well as HSP-based vaccines, further expand therapeutic opportunities across cancer subtypes. Collectively, these approaches highlight the growing therapeutic relevance of disrupting interconnected HSP networks rather than targeting individual chaperones in isolation. Conclusions: Future development of heat shock protein-targeted therapies will require a deeper understanding of HSP-mediated chemoresistance. Clinical trial and drug development approaches may benefit from combination or multi-targeted strategies that simultaneously disrupt multiple components of the heat shock protein network to achieve more durable anticancer responses. Full article

The design of multitargeted drug candidates has recently emerged as a highly attractive area of research. Numerous heterometallic compounds have been developed to enhance both the biological efficacy and physicochemical properties of monometallic metallodrugs. Combining classical transition metals with established antitumor activity, such as Pt, Ru, and Au, with other metal-based fragments offers the potential to generate complex compounds with improved pharmacokinetic and pharmacodynamic profiles. Incorporating different bioactive metal cations within a single molecular framework may enhance anticancer activity through metal-specific interactions with distinct biological targets or through improved physicochemical characteristics of the resulting heteronuclear complexes. Recent studies have underscored the significant progress and promising impact of this multitargeted strategy, particularly in systems that combine ruthenium with other biologically active metal centers. This approach may enable selective biological targeting and help overcome drug resistance. This review compiles and analyzes reported ruthenium-based heteronuclear complexes, offering a comprehensive and critical assessment of recent advances in the rational design and synthesis of novel multinuclear compounds as potential chemotherapeutic agents. Particular emphasis is placed on understanding structure–activity relationships, mechanistic pathways, and the role of metal–metal and metal–ligand interactions in modulating biological responses. The findings summarized herein highlight the remarkable efficacy of a wide range of multinuclear ruthenium anticancer complexes and support the hypothesis that synergistic and/or cooperative interactions between distinct metal-based fragments can significantly enhance pharmacological performance, including improved selectivity, stability, and cellular uptake. Furthermore, emerging insights into their modes of action, resistance profiles, and potential for targeted delivery underscore their promise as viable alternatives to conventional therapies. Overall, this dynamic and rapidly evolving field is poised to inspire continued interdisciplinary research and drive the development of next-generation metallodrugs with improved therapeutic indices and clinical potential. Full article

Cancer remains one of the leading causes of morbidity and mortality worldwide, and despite major advances in surgery, chemotherapy, radiotherapy, and immunotherapy, important therapeutic limitations persist, including systemic toxicity, therapeutic resistance, and poor drug penetration into hypoxic tumor regions. These challenges have renewed interest in alternative biological strategies, particularly the use of bacteria and bacterial toxins as antitumor agents. Certain bacterial species possess intrinsic tumor-targeting properties, including the ability to selectively colonize hypoxic and necrotic regions of solid tumors that are poorly accessible to conventional therapies. This review provides a comprehensive analysis of the mechanisms underlying bacteria-mediated anticancer activity, including selective tumor colonization, direct oncolysis, immune activation, and toxin-mediated cytotoxicity. Both obligate anaerobes (e.g., Clostridium and Bifidobacterium) and facultative anaerobes (e.g., Salmonella, Escherichia coli, and Listeria monocytogenes) are examined for their tumor-targeting potential. In addition, we discuss the oncological applications of several bacterial toxins and toxin-derived therapeutic constructs, including Cytolysin A (ClyA), Clostridium difficile toxin B (TcdB), diphtheria toxin, Pseudomonas aeruginosa exotoxin A, and Clostridium perfringens enterotoxin (CPE). Emerging strategies such as recombinant immunotoxins and bacterial-directed enzyme prodrug therapy (BDEPT) are also reviewed. Finally, current translational challenges, including pharmacokinetic limitations, immune clearance, and biosafety considerations, are analyzed, highlighting future directions for integrating bacteria-based platforms into next-generation cancer therapies. This approach reflects the growing interest in microbial strategies for oncology and underscores the potential of bacteria and their toxins as innovative tools in the development of targeted anticancer therapies. Full article

Marine-derived natural products are increasingly recognized for their therapeutic potential in cancer and other chronic diseases. Despite significant advances, current cancer treatments remain challenged by toxicity, drug resistance, and limited survival benefits. Natural compounds offer promising alternatives due to their multi-target mechanisms and favorable safety profiles. Among them, Spirulina, a filamentous cyanobacterium, stands out for its rich composition and diverse biological activities. Its anticancer effects involve apoptosis induction via intrinsic and extrinsic pathways, cell cycle arrest at G1/S or G2/M phases, inhibition of angiogenesis through the VEGF/VEGFR2 axis, and suppression of epithelial–mesenchymal transition. These activities are mainly attributed to C-phycocyanin, allophycocyanin, phenolic compounds, and immunomodulatory polysaccharides. Spirulina also exhibits potent immunomodulatory effects by enhancing natural killer cell activity, promoting M1 macrophage polarization, and regulating Th1 and Th17 cytokine responses, highlighting its potential as both an immunotherapeutic and chemoprotective agent. Moreover, preclinical findings suggest it may reduce chemotherapy-associated side effects. However, translation into clinical therapy remains limited by low bioavailability, lack of standardized extracts, and scarce clinical evidence. This review summarizes current mechanistic and immunological insights and highlights the need for optimized formulations, defined dosing strategies, and well-designed clinical trials to validate Spirulina’s potential in cancer treatment. Full article

Cancer remains a leading cause of morbidity and mortality globally, with current therapies often limited by toxicity, drug resistance, and reduced efficacy in advanced stages. Medicinal plants represent important sources of bioactive compounds (BACs) with anticancer and chemopreventive potential; however, their successful application is strongly influenced by extraction strategies that determine phytochemical recovery and downstream biological activity. This review evaluates solvent-based extraction techniques used to extract BACs from medicinal plants with reported anticancer properties, synthesizing peer-reviewed articles from PubMed and Google Scholar published between 2020 and 2025. Solvent-based methods, including Soxhlet and maceration, were most widely applied due to their operational simplicity and the preservation of structurally diverse metabolites while percolation, decoction, infusion, and hydro-distillation were sparsely utilized. Extraction strategy and solvent polarity emerged as primary factors shaping phytochemical profiles, with phenolics, flavonoids, alkaloids, and terpenoids identified as dominant classes. Reported half maximal inhibitory concentration (IC₅₀) ranged from highly potent (0.12 µg/mL) to weak (30,000 µg/mL), reflecting variability driven by extraction parameters and plant matrix complexity. Anticancer mechanisms commonly involved apoptosis induction, cell-cycle arrest, reactive oxygen species-mediated cytotoxicity, and inhibition of proliferative signaling pathways across breast, cervical, colon, lung, liver, and prostate cancer models. Although solvent-based extraction approaches remain widely used, their context-dependent nature and lack of standardization limit reproducibility. Overall, anticancer and chemotherapeutic efficacy is primarily governed by BAC composition, while extraction methods act as upstream modulators. Future progress requires phytochemical-informed, standardized workflows supported by hybrid extraction systems, AI-assisted optimization, and advanced bioavailability and delivery systems to enable reproducible and clinically relevant translation of plant-derived chemotherapeutics. Full article

Background: Breast cancer (BC) remains the most prevalent malignancy among women worldwide, with one in eight at risk during their lifetime. Platinum-based chemotherapeutic drugs, despite of their binding to the DNA of cancer cells, are plagued by toxicity and resistance, necessitating the need for safer and more effective alternatives, such as organometallic complexes. Both synthetic organometallic complexes and natural compounds have attracted attention in this regard. Organotin(IV) complexes are promising chemotherapeutics due to their structural versatility and bioactivity, while vitamins such as Vitamin D (VD) and Vitamin E (VE) exhibit antiproliferative, anti-inflammatory, and antioxidant properties, making them valuable candidates for combination therapy. Methodology: In this study, six novel organotin(IV) dithiocarbamate complexes [LMe₃Sn (Complex 1), LBu₃Sn (Complex 2), LPh₃Sn (Complex 3), LMe₂SnCl (Complex 4), LBu₂SnCl (Complex 5), and L₂Me₂Sn (Complex 6), where L = (E)-4-styrylpiperazine-1-carbodithioate], were synthesized and characterized by FT-IR, ¹H-, ¹³C-NMR, and elemental analysis. Results: Structural studies confirmed penta- and hexacoordination geometries. In silico docking against six BC-related proteins identified Complexes 2 and 4 with both vitamins as promising candidates, exhibiting strong binding affinities, with stable interaction profiles. However, integration of pharmacokinetic, antioxidant, and anti-inflammatory analyses highlighted Complex 4 with both vitamins as the most potent candidate owing to its superior ADME characteristics and balanced biological properties. Subsequent in vitro assays confirmed these findings, as Complex 4 demonstrated strong cytotoxic activity against both MCF-7 (>1.16-fold) and MDA-MB-231 (>1.46-fold) cell lines, surpassing the efficacy of cisplatin. Remarkably, co-administration of VD or VE with Complex 4 further enhanced its anticancer potential, with Chou–Talalay combination index values < 1 (0.66–0.91) indicating a synergistic interaction. Conclusions: Collectively, these results identify Complex 4 as a promising lead compound, and its synergistic activity with natural vitamins may promote cell death, likely through apoptosis induction and modulation of oxidative stress, underscoring its potential as an effective and less toxic therapeutic strategy for breast cancer management. Full article

Cancer ranks as one of the top causes of death worldwide, and the World Health Organisation (WHO) estimates an increase of up to 55% in cases over the next 15 years, reaching 300 million cases worldwide. Current approaches to the treatment of cancer, such as chemotherapy and radiation therapy, have been used with continuous significant advancements. However, these conventional methods have harmful side effects that can last a lifetime. Today, there is growing interest in developing alternative cancer therapies from natural products or complementary medicine. One of the natural sources that has shown promise as an anticancer agent is honey, which has long been applied as a complementary medicine, and its beneficial health effects on various diseases in both animal and human models have been widely studied. Malaysian honey, such as Tualang, pineapple, Gelam, Kelulut, and Acacia, possesses a rich composition of phytochemicals, including polyphenols and flavonoids, which are reported to have promising anticancer properties. Examples of the phytochemicals highlighted in this review are phenolic acid, syringic acid, salicylic acid, p-coumaric acid, gallic acid, benzoic acid, caffeic acid, chrysin and its derivatives, kaempferol, fisetin, catechin, apigenin, quercetin, acacetin, pinocembrin, pinobanksin, hesperetin, naringenin, vitexin, isoorientin, xanthohumol, and galangin. This review highlights the anticancer mechanisms and molecular pathways of the phytochemicals found in Malaysian honey, focusing on their antioxidant effects, induction of mitochondrial-mediated apoptosis, inhibition of angiogenesis and metastasis, and suppression of cancer cell proliferation. The findings of various studies published in the past five years are collated to understand their mechanisms of action. Full article

Temozolomide and dacarbazine are untargeted anticancer prodrugs that have been widely employed in the treatment of melanoma and glioblastoma. These agents decompose into a short-lived monomethyl triazene intermediate, culminating in the release of a methyl diazonium cation that serves as the DNA-alkylating species responsible for tumour destruction. However, due to their high chemical lability, these agents have been associated with chemotherapy resistance, mutagenicity, tumour relapse, and significant off-target toxicity. One promising strategy towards the resolution of these limitations involves the design of arylmethyl triazene prodrugs, which enable targeted tumour-specific drug delivery. This review explores the various approaches used to selectively deliver alkyl aryl triazenes as alternatives to current therapies. It highlights early chemical strategies such as N-acylation and etherification of monomethyl triazenes, along with associated kinetic studies. The selective activation of novel triazenes in murine and human melanoma cells through a tyrosinase-responsive promoiety is discussed. Recent progress in nitroaromatic-based prodrugs designed to exploit the hypoxic microenvironment of glioblastoma is also examined. Additionally, we summarise the development of combi-triazenes and their underlying chemistries, which enable the simultaneous release of two active therapeutic agents. Full article