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32 pages, 2108 KiB  
Review
Phytochemical Composition and Multifunctional Applications of Ricinus communis L.: Insights into Therapeutic, Pharmacological, and Industrial Potential
by Tokologo Prudence Ramothloa, Nqobile Monate Mkolo, Mmei Cheryl Motshudi, Mukhethwa Michael Mphephu, Mmamudi Anna Makhafola and Clarissa Marcelle Naidoo
Molecules 2025, 30(15), 3214; https://doi.org/10.3390/molecules30153214 (registering DOI) - 31 Jul 2025
Abstract
Ricinus communis (Euphorbiaceae), commonly known as the castor oil plant, is prized for its versatile applications in medicine, industry, and agriculture. It features large, deeply lobed leaves with vibrant colours, robust stems with anthocyanin pigments, and extensive root systems for nutrient absorption. Its [...] Read more.
Ricinus communis (Euphorbiaceae), commonly known as the castor oil plant, is prized for its versatile applications in medicine, industry, and agriculture. It features large, deeply lobed leaves with vibrant colours, robust stems with anthocyanin pigments, and extensive root systems for nutrient absorption. Its terminal panicle-like inflorescences bear monoecious flowers, and its seeds are enclosed in prickly capsules. Throughout its various parts, R. communis harbours a diverse array of bioactive compounds. Leaves contain tannins, which exhibit astringent and antimicrobial properties, and alkaloids like ricinine, known for anti-inflammatory properties, as well as flavonoids like rutin, offering antioxidant and antibacterial properties. Roots contain ellagitannins, lupeol, and indole-3-acetic acid, known for anti-inflammatory and liver-protective effects. Seeds are renowned for ricin, ricinine, and phenolic compounds crucial for industrial applications such as biodegradable polymers. Pharmacologically, it demonstrates antioxidant effects from flavonoids and tannins, confirmed through minimum inhibitory concentration (MIC) assays for antibacterial activity. It shows potential in managing diabetes via insulin signalling pathways and exhibits anti-inflammatory properties by activating nuclear factor erythroid 2-related factor 2 (Nrf2). Additionally, it has anti-fertility effects and potential anticancer activity against cancer stem cells. This review aims to summarize Ricinus communis’s botanical properties, therapeutic uses, chemical composition, pharmacological effects, and industrial applications. Integrating the current knowledge offers insights into future research directions, emphasizing the plant’s diverse roles in agriculture, medicine, and industry. Full article
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20 pages, 2717 KiB  
Article
Unlocking the Potential of Gracilaria chilensis Against Prostate Cancer
by Verónica Torres-Estay, Lorena Azocar, Camila Schmidt, Macarena Aguilera-Olguín, Catalina Ramírez-Santelices, Emilia Flores-Faúndez, Paula Sotomayor, Nancy Solis, Daniel Cabrera, Loretto Contreras-Porcia, Francisca C. Bronfman and Alejandro S. Godoy
Plants 2025, 14(15), 2352; https://doi.org/10.3390/plants14152352 (registering DOI) - 31 Jul 2025
Abstract
Prostate cancer (PCa) is the second leading cause of cancer-related death among men in most Western countries. Current therapies for PCa are limited, often ineffective, and associated with significant side effects. As a result, there is a growing interest in exploring new therapeutic [...] Read more.
Prostate cancer (PCa) is the second leading cause of cancer-related death among men in most Western countries. Current therapies for PCa are limited, often ineffective, and associated with significant side effects. As a result, there is a growing interest in exploring new therapeutic agents, particularly from the polyphyletic group of algae, which offers a promising source of compounds with anticancer properties. Our research group has focused on investigating the effects of a novel oleoresin from Gracilaria chilensis, known as Gracilex®, as a potential therapeutic agent against PCa using both in vitro and in vivo models. Our findings indicate that Gracilex® exhibits a time- and dose-dependent inhibitory effect on cell survival in LNCaP and PC-3 PCa, reducing viability by over 50% and inducing apoptosis, as evidenced by a significant increase in activated caspase-3 expression in both cell lines. Moreover, Gracilex® significantly reduces the proliferation rate of both LNCaP and PC-3 prostate cancer cell lines, as evidenced by a marked decrease in the growth curve slope (p = 0.0034 for LNCaP; p < 0.0001 for PC-3) and a 40–50% reduction in the proportion of Ki-67-positive PCa cells. In addition, Gracilex® significantly reduces in vitro cell migration and invasion in LNCaP and PC-3 cell lines. Lastly, Gracilex® inhibits tumor growth in an in vivo xenograft model, an effect that correlates with the reduced PCa cell proliferation observed in tumor tissue sections. Collectively, our data strongly support the broad antitumoral effects of Gracilex® on PCa cells in vitro and in vivo. These findings advance our understanding of its potential therapeutic role in PCa and highlight the relevance of further investigating algae-derived compounds for cancer treatment. Full article
(This article belongs to the Section Plant Genetics, Genomics and Biotechnology)
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28 pages, 9865 KiB  
Article
Enhanced Stability of Multi-Functionalized Gold Nanoparticles and Potential Anticancer Efficacy on Human Cervical Cancer Cells
by Aurora Mocanu, Madalina Anca Ujica, Ossi Horovitz, Gheorghe Tomoaia, Olga Soritau, Cristina Teodora Dobrota, Cristina Roxana Popa, Attila Kun, Horea-Rares-Ciprian Benea, Ionel Marius Mang, Gheorghe Borodi, Viorica Raischi, Marius Roman, Lucian Cristian Pop and Maria Tomoaia-Cotisel
Biomedicines 2025, 13(8), 1861; https://doi.org/10.3390/biomedicines13081861 - 31 Jul 2025
Abstract
Objectives: In this research study, we introduce a novel approach to develop an innovative nanocarrier system comprising gold nanoparticles (GNPs) loaded with doxorubicin (D) in combination with natural molecules, such as trans-resveratrol (R), piperine (P), and icariin (Ic), against human cervical cancer. The [...] Read more.
Objectives: In this research study, we introduce a novel approach to develop an innovative nanocarrier system comprising gold nanoparticles (GNPs) loaded with doxorubicin (D) in combination with natural molecules, such as trans-resveratrol (R), piperine (P), and icariin (Ic), against human cervical cancer. The final objective is to improve the anticancer efficacy of doxorubicin on HeLa and CaSki cell lines. Methods: Resveratrol was also used for the synthesis of GNP_R1 nanoparticles. Multi-functional GNPs loaded with D, R, P, and Ic (e.g., GNP_R1@D/R/P/Ic) were successfully prepared and fully characterized by SPR, TEM, HR-TEM, XRD, AFM, DLS, and zeta potential. They were investigated for in vitro stability in various biological media. The cytotoxicity activity was tested on HeLa and CaSki cell lines, using the MTT assay, for their applications as anticancer agents. Results: Our results demonstrate that the novel multi-functional GNPs (such as GNP_R1@D/R and GNP_R1@D/R/P/Ic) can effectively target the cervical cancer cells, improving the bioavailability of therapeutic agents and enhancing their cytotoxicity against cervical cancer cells. In vitro assessments demonstrated that the multi-functional GNPs exhibited improved stability and potential anticancer efficacy on human cervical cancer cells. Conclusions: The described strategy connects the benefits of biomolecules with functional nanoparticles toward the development of various GNP_R1@D/R/P/Ic nanocarriers for their applications as anticancer agents against human cervical cancer. This study provides compelling evidence that the innovative nanoparticles can enhance the therapeutic efficacy of doxorubicin against cervical cancer and offer a more advantageous alternative compared to doxorubicin monotherapy. Full article
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60 pages, 6122 KiB  
Review
Isorhamnetin: Reviewing Recent Developments in Anticancer Mechanisms and Nanoformulation-Driven Delivery
by Juie Nahushkumar Rana, Kainat Gul and Sohail Mumtaz
Int. J. Mol. Sci. 2025, 26(15), 7381; https://doi.org/10.3390/ijms26157381 - 30 Jul 2025
Abstract
Natural compounds, particularly flavonoids, have emerged as promising anticancer agents due to their various biological activities and no or negligible toxicity towards healthy tissues. Among these, isorhamnetin, a methylated flavonoid, has gained significant attention for its potential to target multiple cancer hallmarks. This [...] Read more.
Natural compounds, particularly flavonoids, have emerged as promising anticancer agents due to their various biological activities and no or negligible toxicity towards healthy tissues. Among these, isorhamnetin, a methylated flavonoid, has gained significant attention for its potential to target multiple cancer hallmarks. This review comprehensively explores the mechanisms by which isorhamnetin exerts its anticancer effects, including cell cycle regulation, apoptosis, suppression of metastasis and angiogenesis, and modulation of oxidative stress and inflammation. Notably, isorhamnetin arrests cancer cell proliferation by regulating cyclins, and CDKs induce apoptosis via caspase activation and mitochondrial dysfunction. It inhibits metastatic progression by downregulating MMPs, VEGF, and epithelial–mesenchymal transition (EMT) markers. Furthermore, its antioxidant and anti-inflammatory properties mitigate reactive oxygen species (ROS) and pro-inflammatory cytokines, restricting cancer progression and modulating tumor microenvironments. Combining isorhamnetin with other treatments was also discussed to overcome multidrug resistance. Importantly, this review integrates the recent literature (2022–2024) and highlights isorhamnetin’s roles in modulating cancer-specific signaling pathways, immune evasion, tumor microenvironment dynamics, and combination therapies. We also discuss nanoformulation-based strategies that significantly enhance isorhamnetin’s delivery and bioavailability. This positions isorhamnetin as a promising adjunct in modern oncology, capable of improving therapeutic outcomes when used alone or in synergy with conventional treatments. The future perspectives and potential research directions were also summarized. By consolidating current knowledge and identifying critical research gaps, this review positions Isorhamnetin as a potent and versatile candidate in modern oncology, offering a pathway toward safer and more effective cancer treatment strategies. Full article
(This article belongs to the Special Issue The Role of Natural Compounds in Cancer and Inflammation, 2nd Edition)
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28 pages, 2898 KiB  
Review
Chemical Composition and Biological Activities of Pelargonium sp.: A Review with In Silico Insights into Potential Anti-Inflammatory Mechanism
by Diana Celi, Karina Jimenes-Vargas, António Machado, José Miguel Álvarez-Suárez and Eduardo Tejera
Molecules 2025, 30(15), 3198; https://doi.org/10.3390/molecules30153198 (registering DOI) - 30 Jul 2025
Abstract
The Pelargonium genus, encompassing over 280 species, remains markedly underexplored despite extensive traditional use for respiratory, gastrointestinal, and dermatological disorders. This review of aqueous, alcoholic, and hydroalcoholic extracts reveals critical research gaps: only 10 species have undergone chemical characterization, while 17 have been [...] Read more.
The Pelargonium genus, encompassing over 280 species, remains markedly underexplored despite extensive traditional use for respiratory, gastrointestinal, and dermatological disorders. This review of aqueous, alcoholic, and hydroalcoholic extracts reveals critical research gaps: only 10 species have undergone chemical characterization, while 17 have been evaluated for biological activities. Phytochemical analysis identified 252 unique molecules across all studies, with flavonoids emerging as the predominant class (n = 108). Glycosylated derivatives demonstrated superior bioactivity profiles compared to non-glycosylated analogs. Phenolic acids (n = 43) and coumarins (n = 31) represented additional major classes. Experimental studies primarily documented antioxidant, antibacterial, and anti-inflammatory effects, with emerging evidence for antidiabetic, anticancer, and hepatoprotective activities. However, methodological heterogeneity across studies limits comparative analysis and comprehensive understanding. In silico target prediction analysis was performed on 197 high-confidence molecular structures. Glycosylated flavonols, anthocyanidins, flavones, and coumarins showed strong predicted interactions with key inflammatory targets (ALOX15, ALOX5, PTGER4, and NOS2) and metabolic regulators (GSK3A and PI4KB), providing mechanistic support for observed therapeutic effects and suggesting potential applications in chronic inflammatory and metabolic diseases. These findings underscore the substantial therapeutic potential of underexplored Pelargonium species and advocate for systematic research employing untargeted metabolomics, standardized bioassays, and compound-specific mechanistic validation to fully unlock the pharmacological potential of this diverse genus. Full article
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24 pages, 2509 KiB  
Review
Potential Applications and Risks of Supranutritional Selenium Supplementation in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Critical Review
by Chuanming Liu, Ke Chen, Zijian Xu, Lianshun Wang, Yinhua Zhu, Zhengquan Yu, Tong Li and Jiaqiang Huang
Nutrients 2025, 17(15), 2484; https://doi.org/10.3390/nu17152484 - 30 Jul 2025
Viewed by 200
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the most prevalent chronic diseases in the world, lacking specific pharmacological interventions or well-established treatments. MASLD involves intricate pathological mechanisms characterized by oxidative stress and robust inflammatory responses. Selenium, an essential trace element, plays [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the most prevalent chronic diseases in the world, lacking specific pharmacological interventions or well-established treatments. MASLD involves intricate pathological mechanisms characterized by oxidative stress and robust inflammatory responses. Selenium, an essential trace element, plays a critical role in antioxidation, regulation of inflammation, anticancer activity, and so on. Recent studies have reported that supplementation with selenium could alleviate MASLD and associated hepatic disorders, while excessive consumption may result in insulin resistance or even selenosis. Therefore, supranutritional selenium supplementation can be more suitable for the therapy and prevention of MASLD. This paper comprehensively reviews research about selenium and MASLD to highlight the potential applications and risks of supranutritional selenium supplementation in MASLD, following three steps: conducting a search, reviewing research articles and reviews, and discussing results. The keywords for the search include but are not limited to selenium, MASLD, supranutritional, hepatic diseases, selenoproteions, and selenium nanoparticles (SeNPs). We have reached the following conclusions: supranutritional selenium supplementation exhibits promising potential as a strategy to treat MASLD, but there are still some risks, depending on the dose and form of selenium; evaluating MASLD severity and selenium nutritional status accurately, as well as supplementing with superior forms of selenium (e.g., organic selenium and SeNPs), can further ensure the safety and efficacy of selenium supplementation. However, relationships between selenium homeostasis disorders and the occurrence and development of MASLD have not been fully elucidated. Methods for comprehensively assessing selenium status and mechanisms of selenosis require further investigation and research. Full article
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19 pages, 4058 KiB  
Article
Antitumor Activity of Ruditapes philippinarum Polysaccharides Through Mitochondrial Apoptosis in Cellular and Zebrafish Models
by Mengyue Liu, Weixia Wang, Haoran Wang, Shuang Zhao, Dongli Yin, Haijun Zhang, Chunze Zou, Shengcan Zou, Jia Yu and Yuxi Wei
Mar. Drugs 2025, 23(8), 304; https://doi.org/10.3390/md23080304 - 29 Jul 2025
Viewed by 91
Abstract
Colorectal cancer (CRC) remains a predominant cause of global cancer-related mortality, highlighting the pressing demand for innovative therapeutic strategies. Natural polysaccharides have emerged as promising candidates in cancer research due to their multifaceted anticancer mechanisms and tumor-suppressive potential across diverse malignancies. In this [...] Read more.
Colorectal cancer (CRC) remains a predominant cause of global cancer-related mortality, highlighting the pressing demand for innovative therapeutic strategies. Natural polysaccharides have emerged as promising candidates in cancer research due to their multifaceted anticancer mechanisms and tumor-suppressive potential across diverse malignancies. In this study, we enzymatically extracted a polysaccharide, named ERPP, from Ruditapes philippinarum and comprehensively evaluated its anti-colorectal cancer activity. We conducted in vitro assays, including CCK-8 proliferation, clonogenic survival, scratch wound healing, and Annexin V-FITC/PI apoptosis staining, and the results demonstrated that ERPP significantly inhibited HT-29 cell proliferation, suppressed colony formation, impaired migratory capacity, and induced apoptosis. JC-1 fluorescence assays provided further evidence of mitochondrial membrane potential (MMP) depolarization, as manifested by a substantial reduction in the red/green fluorescence ratio (from 10.87 to 0.35). These antitumor effects were further validated in vivo using a zebrafish HT-29 xenograft model. Furthermore, ERPP treatment significantly attenuated tumor angiogenesis and downregulated the expression of the vascular endothelial growth factor A (Vegfaa) gene in the zebrafish xenograft model. Mechanistic investigations revealed that ERPP primarily activated the mitochondrial apoptosis pathway. RT-qPCR analysis showed an upregulation of the pro-apoptotic gene Bax and a downregulation of the anti-apoptotic gene Bcl-2, leading to cytochrome c (CYCS) release and caspase-3 (CASP-3) activation. Additionally, ERPP exhibited potent antioxidant capacity, achieving an 80.2% hydroxyl radical scavenging rate at 4 mg/mL. ERPP also decreased reactive oxygen species (ROS) levels within the tumor cells, thereby augmenting anticancer efficacy through its antioxidant activity. Collectively, these findings provide mechanistic insights into the properties of ERPP, underscoring its potential as a functional food component or adjuvant therapy for colorectal cancer management. Full article
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15 pages, 787 KiB  
Article
Beyond Treatment Decisions: The Predictive Value of Comprehensive Geriatric Assessment in Older Cancer Patients
by Eleonora Bergo, Marina De Rui, Chiara Ceolin, Pamela Iannizzi, Chiara Curreri, Maria Devita, Camilla Ruffini, Benedetta Chiusole, Alessandra Feltrin, Giuseppe Sergi and Antonella Brunello
Cancers 2025, 17(15), 2489; https://doi.org/10.3390/cancers17152489 - 28 Jul 2025
Viewed by 122
Abstract
Background: Comprehensive Geriatric Assessment (CGA) is essential for evaluating older cancer patients, but significant gaps persist in both research and clinical practice. This study aimed (I) to identify the CGA elements that most influence anti-cancer treatment decisions in older patients and (II) [...] Read more.
Background: Comprehensive Geriatric Assessment (CGA) is essential for evaluating older cancer patients, but significant gaps persist in both research and clinical practice. This study aimed (I) to identify the CGA elements that most influence anti-cancer treatment decisions in older patients and (II) to explore the predictive value of CGA components for mortality. Methods: This observational study included older patients with newly diagnosed, histologically confirmed solid or hematological cancers, recruited consecutively from 2003 to 2023. Participants were followed for four years. The data collected included CGA measures of functional (Activities of Daily Living-ADL), cognitive (Mini-Mental State Examination-MMSE), and emotional (Geriatric Depression Scale-GDS) domains. Patients were categorized into frail, vulnerable, or fit groups based on Balducci’s criteria. Statistical analyses included decision tree modeling and Cox regression to identify predictors of mortality. Results: A total of 7022 patients (3222 females) were included, with a mean age of 78.3 ± 12.9 years. The key CGA factors influencing treatment decisions were ADL (first step), cohabitation status (second step), and age (last step). After four years, 21.9% patients had died. Higher GDS scores (OR 1.04, 95% CI 1.01–1.07, p = 0.04) were independently associated with survival in men and living with family members (OR 1.67, 95% CI 1.35–2.07, p < 0.001) in women. Younger patients (<77 years) showed both MMSE and GDS as significant risk factors for mortality. Conclusions: Functional capacity, cohabitation status, and GDS scores are crucial for guiding treatment decisions and predicting mortality in older cancer patients, emphasizing the need for a multidimensional geriatric assessment. Full article
(This article belongs to the Section Clinical Research of Cancer)
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15 pages, 1274 KiB  
Review
Engineered Bifidobacterium Strains Colonization at Tumor Sites: A Novel Approach to the Delivery of Cancer Treatments
by Rhea Amonkar, Ashley Ann Uy, Pablo Ramirez, Harina Patel, Jae Jin Jeong, Nicole Oyinade Shoyele, Vidhi Vaghela and Ashakumary Lakshmikuttyamma
Cancers 2025, 17(15), 2487; https://doi.org/10.3390/cancers17152487 - 28 Jul 2025
Viewed by 221
Abstract
Bacteria-mediated cancer therapy represents a novel and promising strategy for targeted drug delivery to solid tumors. Multiple studies have demonstrated that various Bifidobacterium species can selectively colonize the hypoxic microenvironments characteristic of solid tumors. Leveraging this property, Bifidobacterium has been explored as a [...] Read more.
Bacteria-mediated cancer therapy represents a novel and promising strategy for targeted drug delivery to solid tumors. Multiple studies have demonstrated that various Bifidobacterium species can selectively colonize the hypoxic microenvironments characteristic of solid tumors. Leveraging this property, Bifidobacterium has been explored as a delivery vector for a range of anti-cancer approaches such as immunotherapy, nanoformulated chemotherapeutics, and gene therapy. Notably, anti-angiogenic genes such as endostatin and tumstatin have been successfully delivered to colorectal tumors using Bifidobacterium infantis and Bifidobacterium longum, respectively. Additionally, Bifidobacterium bifidum has been employed to transport doxorubicin and paclitaxel nanoparticles to breast and lung tumor sites. Furthermore, both Bifidobacterium longum and Bifidobacterium bifidum have been utilized to deliver nanoparticles that act as synergistic agents for high-intensity focused ultrasound (HIFU) therapy, significantly enhancing tumor ablation, particularly in triple-negative breast cancer (TNBC) models. While these pre-clinical findings are highly encouraging, further clinical research is essential. Specifically, studies are needed to investigate the colonization dynamics of different Bifidobacterium species across various tumor types and to evaluate their potential in delivering diverse cancer therapies in human patients. Full article
(This article belongs to the Special Issue Advances in Drug Delivery for Cancer Therapy)
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25 pages, 14674 KiB  
Article
Eco-Friendly Silver Nanoparticles Synthesis Method Using Medicinal Plant Fungal Endophytes—Biological Activities and Molecular Docking Analyses
by Harish Chandra, Sagar Vishwakarma, Nilesh Makwana, Arun S. Kharat, Vijeta Chaudhry, Sumit Chand, Rajendra Prasad, Soban Prakash, Annapurna Katara, Archana Yadav, Manisha Nigam and Abhay Prakash Mishra
Biology 2025, 14(8), 950; https://doi.org/10.3390/biology14080950 - 28 Jul 2025
Viewed by 342
Abstract
The integration of nanotechnology and green synthesis strategies provides innovative solutions in biomedicine. This study focuses on the biofabrication of silver nanoparticles (AgNPs) using Corynespora smithii, an endophytic fungus isolated from Bergenia ciliata. The eco-friendly synthesis process employed fungal extracts as [...] Read more.
The integration of nanotechnology and green synthesis strategies provides innovative solutions in biomedicine. This study focuses on the biofabrication of silver nanoparticles (AgNPs) using Corynespora smithii, an endophytic fungus isolated from Bergenia ciliata. The eco-friendly synthesis process employed fungal extracts as reducing and stabilizing agents thereby minimizing the need for hazardous chemicals. The AgNPs demonstrated strong potent biological activities, showcasing significant antioxidant, antibacterial, and anticancer properties. The antibacterial efficacy was demonstrated against various Gram-positive and Gram-negative bacteria, while cytotoxicity on the A549 lung cancer cell line revealed an IC50 value of 10.46 µg/mL. A molecular docking analysis revealed interactions between the major bioactive compound, dimethylsulfoxonium formylmethylide, and the pathogenic proteins, Staphylococcus aureus and Salmonella typhi, displaying moderate binding affinities. Furthermore, the ADME analysis of dimethylsulfoxonium formylmethylide indicated favourable pharmacokinetic properties, including high gastrointestinal absorption, minimal lipophilicity, and low potential for drug–drug interactions, making it a promising candidate for oral drug formulations. These findings further support the compound’s suitability for biomedical applications. This research emphasizes the potential of C. smithii as a sustainable source for synthesizing bioactive nanoparticles, paving the way for their application in developing novel therapeutic agents. This study highlights the significance of harnessing endophytic fungi from medicinal plants for sustainable nanotechnology advancements. Full article
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20 pages, 3005 KiB  
Review
EUS-Guided Pancreaticobiliary Ablation: Is It Ready for Prime Time?
by Nina Quirk, Rohan Ahuja and Nirav Thosani
Immuno 2025, 5(3), 30; https://doi.org/10.3390/immuno5030030 - 25 Jul 2025
Viewed by 201
Abstract
Despite advances in surgery, chemotherapy, and radiation treatments for pancreatic ductal adenocarcinoma (PDAC), 5-year survival rates remain at nearly 11%. Cholangiocarcinoma, while not as severe, also possesses similar survival rates. Fewer than 20% of patients are surgical candidates at time of diagnosis; therefore, [...] Read more.
Despite advances in surgery, chemotherapy, and radiation treatments for pancreatic ductal adenocarcinoma (PDAC), 5-year survival rates remain at nearly 11%. Cholangiocarcinoma, while not as severe, also possesses similar survival rates. Fewer than 20% of patients are surgical candidates at time of diagnosis; therefore, it is imperative that alternative therapies are effective for non-surgical patients. There are several thermal ablative techniques, including radiofrequency ablation (RFA), high-intensity focused ultrasound (HIFU), microwave ablation (MWA), alcohol ablation, stereotactic body radiotherapy (SBRT), cryoablation, irreversible electroporation (IRE), biliary intraluminal brachytherapy, and biliary photodynamic therapy (PDT). Emerging literature in animal models and human patients has demonstrated that endoscopic ultrasound (EUS)-guided RFA (EUS-RFA) prevents tumor progression through coagulative necrosis, protein denaturation, and activation of anticancer immunity in local and distant tumor tissue (abscopal effect). RFA treatment has been shown to not only reduce tumor-associated immunosuppressive cells but also increase functional T cells in distant tumor cells not treated with RFA. The remarkable ability to reduce tumor progression and promote tumor microenvironment (TME) remodeling makes RFA a very promising non-surgical therapy technique that has the potential to reduce mortality in this patient population. EUS-RFA offers superior precision and safety compared to other ablation techniques for pancreatic and biliary cancers, due to real-time imaging capabilities and minimally invasive nature. Future research should focus on optimizing RFA protocols, exploring combination therapies with chemotherapy or immunotherapy, and expanding its use in patients with metastatic disease. This review article will explore the current data and underlying pathophysiology of EUS-RFA while also highlighting the role of ablative therapies as a whole in immune activation response. Full article
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16 pages, 1786 KiB  
Article
Repurposing Analysis of Nitroxoline (8-Hydroxy-5-nitroquinoline) as an Antichagasic Compound
by Carlos J. Bethencourt-Estrella, Atteneri López-Arencibia, Isabel M. Calero-Docina, Frieder Fuchs, Patrick Scheid, Jacob Lorenzo-Morales and José E. Piñero
Pharmaceuticals 2025, 18(8), 1106; https://doi.org/10.3390/ph18081106 - 25 Jul 2025
Viewed by 261
Abstract
Background/Objectives: Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, remains a major neglected tropical disease, with over six million cases concentrated, primarily in Latin America. Despite decades of research, treatment continues to rely on two outdated drugs—benznidazole and nifurtimox—both of which [...] Read more.
Background/Objectives: Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, remains a major neglected tropical disease, with over six million cases concentrated, primarily in Latin America. Despite decades of research, treatment continues to rely on two outdated drugs—benznidazole and nifurtimox—both of which exhibit limited efficacy and are associated with severe side effects. In this context, drug repurposing presents a promising strategy to accelerate the development of safer and more effective therapies. Nitroxoline, a hydroxyquinoline compound widely used in Europe to treat bacterial urinary tract infections, has recently garnered attention for its broad-spectrum antimicrobial and anticancer activities. This study evaluated the antitrypanosomal potential of nitroxoline against both epimastigote and intracellular amastigote forms of T. cruzi, demonstrating significantly greater efficacy than benznidazole. Methods: In addition to its antiparasitic activity, we investigated the mechanism of parasite death and found that nitroxoline induces hallmarks of programmed cell death, including chromatin condensation, mitochondrial membrane depolarization, ATP depletion, reactive oxygen species accumulation, and increased membrane permeability. These cellular events are critical for minimizing host tissue inflammation and suggest a safer therapeutic profile. Results: The nitroxoline was shown to induce greater activity than the reference treatment, benznidazole, in addition to triggering events related to apoptotic or silent cell death. Conclusions: Given its established clinical use and favorable safety data, nitroxoline emerges as a strong candidate for further investigation as a repurposed treatment for Chagas disease. Future work should focus on in vivo efficacy, pharmacokinetics, and drug delivery strategies to enhance systemic bioavailability. Full article
(This article belongs to the Special Issue Recent Advancements in the Development of Antiprotozoal Agents)
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21 pages, 319 KiB  
Review
The Role of the Endocannabinoid System in Oncology and the Potential Use of Cannabis Derivatives for Cancer Management in Companion Animals
by Giorgia della Rocca, Alessandra Di Salvo, Erica Salucci, Michela Amadori, Giovanni Re and Cristina Vercelli
Animals 2025, 15(15), 2185; https://doi.org/10.3390/ani15152185 - 24 Jul 2025
Viewed by 184
Abstract
The last decades of research have shown that the endocannabinoid system may be a promising therapeutic target for the pharmacological treatment of cancer in human medicine and possibly in veterinary medicine as well. Compared with the original cells, the expression of gene encoding [...] Read more.
The last decades of research have shown that the endocannabinoid system may be a promising therapeutic target for the pharmacological treatment of cancer in human medicine and possibly in veterinary medicine as well. Compared with the original cells, the expression of gene encoding for receptors and enzymes belonging to the endocannabinoid system has been found to be altered in several tumor types; it has been hypothesized that this aberrant expression may be related to the course of the neoplasm as well as to the patient’s prognosis. Several studies, conducted both in vitro and in vivo, suggest that both endo- and phytocannabinoids can modulate signaling pathways, controlling cell proliferation and survival. In the complex process of carcinogenesis, cannabinoids seem to intervene at different levels by stimulating cell death, inhibiting the processes of angiogenesis and metastasis, and regulating antitumor immunity. Although the molecular mechanisms by which cannabinoids act are not always clear and defined, their synergistic activity with the most used antineoplastic drugs in clinical oncology is showing promising results, thus providing veterinary medicine with alternative therapeutic targets in disease control. This review aims to summarize current knowledge on the potential role of the endocannabinoid system and exogenous cannabinoids in oncology, with specific reference to the molecular mechanisms by which cannabinoids may exert antitumor activity. Additionally, it explores the potential synergy between cannabinoids and conventional anticancer drugs and considers their application in veterinary oncology. Full article
40 pages, 1654 KiB  
Review
Bioactive Plant-Derived Compounds as Novel Perspectives in Oral Cancer Alternative Therapy
by Gabriela Mitea, Verginica Schröder and Irina Mihaela Iancu
Pharmaceuticals 2025, 18(8), 1098; https://doi.org/10.3390/ph18081098 - 24 Jul 2025
Viewed by 306
Abstract
Background: Oral squamous cell carcinoma (OSCC) is one of the most serious forms of cancer in the world. The opportunities to decrease the mortality rate would lie in the possibility of earlier identification of this pathology, and at the same time, the immediate [...] Read more.
Background: Oral squamous cell carcinoma (OSCC) is one of the most serious forms of cancer in the world. The opportunities to decrease the mortality rate would lie in the possibility of earlier identification of this pathology, and at the same time, the immediate approach of anticancer therapy. Furthermore, new treatment strategies for OSCC are needed to improve existing therapeutic options. Bioactive compounds found in medicinal plants could be used to support these strategies. It is already known that they have an increased potential for action and a safety profile; therefore, they could improve the therapeutic effect of classical chemotherapeutic agents in combination therapies. Methodology: This research was based on an extensive review of recently published studies in scientific databases (PubMed, Scopus, and Web of Science). The selection criteria were based on experimental protocols investigating molecular mechanisms, synergistic actions with conventional anticancer agents, and novel formulation possibilities (e.g., nanoemulsions and mucoadhesive films) for the targeted delivery of bioactive compounds in OSCC. Particular attention was given to in vitro, in vivo, translational, and clinical studies that have proven therapeutic relevance. Results: Recent discoveries regarding the effect of bioactive compounds in the treatment of oral cancer were analyzed, with a view to integrating them into oncological practice for increasing therapeutic efficacy and reducing the occurrence of adverse reactions and treatment resistance. Conclusions: Significant progress has been achieved in this review, allowing us to appreciate that the valorization of these bioactive compounds is emerging. Full article
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26 pages, 1809 KiB  
Review
Salt-Adapted Microorganisms: A Promising Resource for Novel Anti-Cancer Drug Discovery
by Longteng Fang, Liping Xu, Marhaba Kader, Tingting Ding, Shiyang Lu, Dong Wang, Amit Raj Sharma and Zhiwei Zhang
Mar. Drugs 2025, 23(8), 296; https://doi.org/10.3390/md23080296 - 24 Jul 2025
Viewed by 419
Abstract
Microorganisms serve as a vital source of natural anticancer agents, with many of their secondary metabolites already employed in clinical oncology. In recent years, salt-adapted microbes, including halophilic and halotolerant species from marine, salt lake, and other high-salinity environments, have gained significant attention. [...] Read more.
Microorganisms serve as a vital source of natural anticancer agents, with many of their secondary metabolites already employed in clinical oncology. In recent years, salt-adapted microbes, including halophilic and halotolerant species from marine, salt lake, and other high-salinity environments, have gained significant attention. Their unique adaptation mechanisms and diverse secondary metabolites offer promising potential for novel anticancer drug discovery. This review consolidated two decades of research alongside current global cancer statistics to evaluate the therapeutic potential of salt-adapted microorganisms. Halophilic and halotolerant species demonstrate significant promise, with their bioactive metabolites exhibiting potent inhibitory effects against major cancer cell lines, particularly in lung and breast cancer. Evidence reveals structurally unique secondary metabolites displaying enhanced cytotoxicity compared to conventional anticancer drugs. Collectively, salt-adapted microorganisms represent an underexplored yet high-value resource for novel anticancer agents, offering potential solutions to chemotherapy resistance and treatment-related toxicity. Full article
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