Search Results (1,968)

Background/Objectives: To improve the response rate of immune checkpoint inhibitors (ICIs), inducing immunogenic cell death (ICD) is a promising approach. Photothermal therapy (PTT) induces immunogenic cell death and activates anti-tumor immunity. While there are various ICD inducers, the difference in ICD induction by various modalities is poorly understood. In this study, we found previously unrecognized advantages of PTT compared to anti-cancer drugs and showed the usefulness of PTT as an anti-cancer drug-free approach to be combined with immunotherapy. Methods: Gold nanorods were synthesized as photothermal agents and added to culture medium or locally administered to tumor tissues. Mitoxantrone (MIT), an ICD inducer, and cisplatin (CDDP), a non-ICD inducer, were compared with PTT. To assess the induction of ICD, the subcellular localization and amounts of high mobility group box 1 (HMGB1) and calreticulin (CRT) were observed using immunofluorescent staining. FM3A tumor-bearing mice were treated with PTT or anti-cancer drugs, and cell death and DAMPs localization in tumor tissues were analyzed. Also, the supra-additive effect of PTT on ICI was observed. Tumor-infiltrating CD8⁺ T cells were examined to evaluate the immune status in tumor tissues. Results: In vivo assays showed that PTT induces HMGB1 release and increased expression of CRT on the cell membrane. Moreover, PTT showed a supra-additive effect in terms of therapeutic effect and anti-tumor activation when combined with an immune checkpoint inhibitor. Conclusions: In this study, we demonstrated that PTT induced ICD-related signaling and improved the response rate of ICI, which means PTT is a promising combination therapy with ICI. Full article

Background/Objectives: Cancer persists as a leading concern in the current medical field, and current therapies are limited by toxicity, cost, and resistance. Targeted inhibition of tubulin polymerization is considered as a promising therapeutic strategy for cancer treatment. Methods: Thirty-one new tubulin polymerization inhibitors were designed via molecular hybridization techniques, and BLI technology was employed to quantitatively investigate their interactions with tubulin. Antiproliferative activities against MCF-7, MDA-MB-231, A549, and HeLa cell lines was evaluated using the CCK8 assay. Apoptosis induction and cell cycle arrest were analyzed by flow cytometry. The anti-tumor activity of compound B6 was validated in a mouse melanoma tumor model. Results: Compounds exhibited varying degrees of antiproliferative activity against four tumor cell lines. Among them, compound B6 was the most promising candidate and displayed strong broad-spectrum anticancer activity with an average IC₅₀ value of 2 μM. The mechanism studies revealed that compound B6 inhibited tubulin polymerization in vitro, disrupted cell microtubule networks, and arrested the cell cycle at G2/M phase. Furthermore, B6 displayed significant in vivo antitumor efficacy in a melanoma tumor model with tumor growth inhibition rates of 70.21% (50 mg/kg). Conclusions: This work shows that B6 is a promising lead compound deserving further investigation as a potential anticancer agent. Full article

Microneedle (MN) technologies have emerged as a groundbreaking platform for transdermal and intradermal drug delivery, offering a minimally invasive alternative to oral and parenteral routes. Unlike passive transdermal systems, MNs allow the permeation of hydrophilic macromolecules, such as peptides, proteins, and vaccines, by penetrating the stratum corneum barrier without causing pain or tissue damage, unlike hypodermic needles. Recent advances in materials science, microfabrication, and biomedical engineering have enabled the development of various MN types, including solid, coated, dissolving, hollow, hydrogel-forming, and hybrid designs. Each type has unique mechanisms, fabrication techniques, and pharmacokinetic profiles, providing customized solutions for a range of therapeutic applications. The integration of 3D printing technologies and stimulus-responsive polymers into MN systems has enabled patches that combine drug delivery with real-time physiological sensing. Over the years, MN applications have grown beyond vaccines to include the delivery of insulin, anticancer agents, contraceptives, and various cosmeceutical ingredients, highlighting the versatility of this platform. Despite this progress, broader clinical and commercial adoption is still limited by issues such as scalable and reliable manufacturing, patient acceptance, and meeting regulatory expectations. Overcoming these barriers will require coordinated efforts across engineering, clinical research, and regulatory science. This review thoroughly summarizes MN technologies, beginning with their classification and drug-delivery mechanisms, and then explores innovations, therapeutic uses, and translational challenges. It concludes with a critical analysis of clinical case studies and a future outlook for global healthcare. By comparing technological progress with regulatory and commercial hurdles, this article highlights the opportunities and limitations of MN systems as a next-generation drug-delivery platform. Full article

Phosphatidylinositol-3-kinases (PI3Ks) constitute an important validated therapeutic class involved in crucial cellular processes, and their dysregulation is associated with cancer initiation and progression. Nonetheless, intrinsic and acquired resistance mechanisms associated with PI3K pathway modulation have underscored the need for alternative therapeutic strategies. In this context, recent studies have shown that simultaneous inhibition of PI3K and histone deacetylases (HDAC) promotes synergistic antitumor effects in different cancer cell lines. HDACs are validated epigenetic targets that are extensively explored in clinical practice and have a pharmacophore with versatility for structural modifications, which facilitates the design of multitarget inhibitors. This review examines the rational design and synthetic evolution of dual PI3K/HDAC inhibitors, an area catalyzed by the development of fimepinostat, the first clinically evaluated agent exhibiting potent and balanced inhibition of both targets. We provide a critical overview of PI3K/HDAC multitarget inhibitors reported in recent years that have progressed to preclinical or clinical investigation, discussing the structural frameworks employed, medicinal chemistry strategies adopted, and structure–activity relationships established. Particular attention is given to advantageous molecular features as well as challenges related to toxicity, pharmacokinetic behavior, and pharmacodynamic modulation. From this comprehensive analysis, we outline key considerations and emerging design principles that may inform the next generation of PI3K/HDAC multitarget drug candidates. Insights derived from the diversity of chemical scaffolds, activity profiles, and selectivity patterns described herein may support the development of innovative therapeutic agents capable of overcoming current limitations in anticancer treatment. Full article

Cotinus coggygria Scop., a member of the Anacardiaceae family, is known for its antiseptic, anti-inflammatory, and antitumor properties. In the present study, the ethyl acetate/water leaf extract of C. coggygria was evaluated for antioxidant and anticancer activities. The extract exhibited strong radical-scavenging potential, effectively neutralizing DPPH, ABTS^•+, and superoxide radicals in a concentration-dependent manner. The cytotoxic effects of the extract on human hepatocellular carcinoma HepG2 cells were also investigated. Flow cytometry revealed significant S-phase cell cycle arrest, while fluorescent microscopy and annexin V-FITC/PI staining demonstrated induction of apoptosis. DNA damage was confirmed by alkaline comet assay. Molecular docking was used to evaluate the binding affinity and inhibitory potential of penta-O-galloyl-β-D-glucose, a representative of gallotannins found in C. coggygria extracts, towards cyclin-dependent kinase 2 and checkpoint kinase 1. A high inhibition ability was demonstrated, which could explain the observed cell cycle block. Collectively, these findings suggest that C. coggygria extract exerts strong antioxidant capacity and selective antiproliferative activity in HepG2 cells. The anticancer effects of C. coggygria extract were associated with DNA damage, cell cycle arrest, disruption of mitochondrial membrane potential, and apoptosis induction. The results show the potential of the herb as a natural therapeutic agent for hepatocellular carcinoma. Full article

Erinacine A, a cyathane diterpenoid derived from the medicinal and edible fungus Hericium erinaceus, is increasingly recognized for its potent neurotrophic and neuroprotective properties. It demonstrates significant therapeutic promise for neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease, primarily by stimulating the synthesis of nerve growth factor (NGF). However, the clinical applicability of erinacine A is currently restricted by its low yield from natural sources and high production costs. This challenge has spurred significant research focused on optimizing its production. This review provides a comprehensive overview of the current advancements in the fermentation-based preparation of erinacine A, including both liquid and solid-state cultivation techniques. Furthermore, we summarize its diverse biological activities, spanning neuroprotection, anticancer, and anti-inflammatory effects, and detail the recent discoveries elucidating its complex biosynthetic pathway. This consolidated overview offers insights into strategies for enhancing its production and supports its ongoing development as a therapeutic agent. Full article

Marine invertebrates are a prime source of biologically active peptides due to their role in humoral immunity. These peptides typically exhibit broad-spectrum functions, including antibacterial, antifungal, anticancer, and immunomodulatory activities. In this report, we describe the identification and biological characterization of five novel bioactive peptides from the marine mollusk Pisania pusio. An extract of P. pusio was analyzed using nanoLC-ESI-MS-MS, and five peptides (PP1–5) were selected via bioinformatic screening as potential antimicrobial and anticancer peptides and subsequently validated experimentally. Among these, PP1, PP2, and PP4 were identified as cryptides derived from the proteolytic cleavage of actin, while PP3 and PP5 are novel peptides with no known protein precursors. All peptides exhibited moderate activity against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Klebsiella pneumoniae with minimum inhibitory concentrations (MICs) predominantly at 100 µM. In contrast, only PP1 and PP5 were active against cancer cells, with PP1 being the most effective against A375 melanoma cells (IC₅₀ = 17.08 µM). This experimental validation confirmed the utility of the integrated in silico/peptidomic pipeline for lead identification. None of these peptides showed significant hemolytic activity or toxicity on fetal lung fibroblasts over 800 μM, demonstrating promising in vitro selectivity. These results highlight the multifunctional nature of P. pusio-derived peptides and their potential as lead compounds for further optimization and development into therapeutic agents against microbial infections and cancer, subject to more comprehensive safety evaluations in relevant models Full article

An unmet challenge in managing breast cancer is treatment failure due to resistance to apoptosis-inducing chemotherapies. Thus, it is important to identify novel non-apoptotic therapeutic agents. Several non-apoptotic programmed cell death pathways utilize specific cellular signaling events to trigger lytic and pro-inflammatory cell death, examples of which are pyroptosis and necroptosis. Our study illustrates that ophiobolin A (OpA) is an anti-cancer agent that triggers lytic cell death in breast cancer cells, including triple-negative breast cancer (TNBC). This study reveals that OpA induces typical pyroptosis-like characteristics, including cellular swelling, plasma membrane rupture, GSDMD cleavage, and release of cytokines in breast cancer cells. However, the additional involvement of RIPK1 and induction of RIPK3 clustering in select cell lines suggest that multiple pathways may be triggered upon OpA treatment. The induction of pro-inflammatory cell death suggests potential applications for OpA in cancer treatment. Full article

Extensively drug-resistant (XDR) bacteria pose a serious global public health threat due to their high levels of resistance to multiple classes of antibiotics. This study aimed to characterize bacterial isolates obtained from clinical samples, evaluate their antibiotic resistance patterns, and investigate the antimicrobial and anticancer potential of essential oils (EOs) and their nanoemulsions (NEs). A total of 175 bacterial isolates were collected from various clinical sources, identified, and subjected to antibiotic susceptibility testing using both conventional methods and the VITEK^® 2 system. Among these, nine isolates were identified as extensively drug-resistant. Among the tested EOs, carvacrol exhibited the strongest antibacterial activity, with minimum inhibitory concentrations (MICs) ranging from 14 to 35 µg/mL, compared to 8 to 19 µg/mL for meropenem. To enhance its stability and efficacy, carvacrol nanoemulsions (CANE) were prepared via ultrasonication and characterized using zeta potential measurements, which indicated a positive surface charge of +14.2 mV, while dynamic light scattering (DLS) analysis revealed a narrow size distribution with a mean hydrodynamic diameter of 411.3 nm. High-resolution transmission electron microscopy (HR-TEM) showed spherical droplets ranging from 18 to 144 nm in size, with an average diameter of 69 ± 28 nm. The nanoemulsion formulation significantly enhanced antibacterial activity, with MICs reduced to 11 ± 0.0–23 ± 0.21 µg/mL, compared to 14 ± 0.13–35 ± 0.11 µg/mL for pure carvacrol oil. Gas chromatography–mass spectrometry (GC–MS) analysis identified major active constituents, including thymol, methoxyphenyl, estragole, and D-limonene, which are likely contributors to the observed antimicrobial and anticancer effects. In addition, carvacrol nanoemulsions demonstrated potent cytotoxicity against multiple human cancer cell lines (HepG2, MCF-7, PC-3, and Caco-2) while showing minimal toxicity toward normal cells. Confocal microscopy further confirmed apoptosis induction in treated cancer cells, suggesting a mitochondria-mediated apoptotic pathway. In conclusion, this study highlights the strong therapeutic potential of essential oils—particularly carvacrol and its nanoemulsion formulation—as dual-action agents exhibiting broad-spectrum antibacterial activity against XDR pathogens and selective cytotoxicity against cancer cells. Full article

Background: Neuroblastoma is the most common extracranial solid malignancy in infants and children. High-risk neuroblastoma patients are commonly treated with temozolomide (TMZ), which typically exhibits a poor therapeutic response. Serotonin, also known as 5-hydroxytryptamine (5-HT), plays various essential functions in the human body. In the central nervous system, it serves as a neurotransmitter. Beyond its physiological roles, 5-HT has recently been identified as a potential growth factor for several human tumors, including gliomas and carcinoid tumors. Recent literature has demonstrated that 5-HT receptor antagonists can inhibit the growth of cancer cells. Furthermore, both 5-HT receptors and their antagonists have been identified as potential anticancer agents, suggesting their significance in the development of new treatment strategies. Objectives: The primary aim of this study was to examine the effects of 5-HT and 5-HT antagonists on tumor (neuroblastoma (SH-SY5Y)) and healthy cells (microglia (HMC3)) and determine the impact of their interaction with the anticancer agent TMZ on cell proliferation/viability and migration. Methods: The study explored the interaction between 5-HT, the 5-HT antagonist granisetron (GRN), the anticancer agent TMZ, and their combinations, specifically assessing their influence on cell proliferation, viability, and migration. Results: As a result, the single and combined applications of 5-HT, TMZ, and GRN, a 5-HT antagonist, inhibited cell growth and proliferation in SH-SY5Y, causing decreased cell viability. Additionally, the combination of 5-HT and GRN increased the efficacy of TMZ. Conclusions: The study findings revealed that 5-HT and 5-HT antagonists may have therapeutic effects by exhibiting antiproliferative effects in SH-SY5Y cells at high concentrations. Full article

Benzoxaboroles have garnered significant interest for their therapeutic potential in various diseases. Among them, 7-propanamide benzoxaborole has served as a new and valuable chemotype for anti-cancer agents, although their definitive intracellular target(s) remains elusive. Herein, three-dimensional quantitative structure–activity relationship (3D-QSAR) was used to systematically investigate the structure–activity relationships (SAR) of a series of 7-propanamide benzoxaboroles. Comparative molecular field analysis (CoMFA, r² = 0.991, q² = 0.626) and comparative molecular similarity indices analysis (CoMSIA, r² = 0.964, q² = 0.605) revealed critical structural determinants of 7-propanamide benzoxaboroles for inhibition of the ovarian cancer cell (SKOV3) proliferation. Based on the guidance of the critical structural determinants, we designed a new benzoxaborole compound 42 with high predicted inhibition activity values. In vitro proliferation assessment showed that compound 42 exhibited superior inhibitory potency to lead compound 1 and comparable activity to compound 41. These findings indicated that the SAR of benzoxaborole compounds through 3D-QSAR can offer valuable theoretical insights for the structural optimization of new benzoxaboroles as anti-SKOV3 agents. Full article

Background: A benzotriazole is a heterocycle frequently used in medicinal chemistry to obtain potent drug candidates, including anticancer agents. Nonetheless, the available literature lacks a comprehensive review of the in vitro and in vivo studies regarding these derivatives. Thus, our study aims to review the preclinical evidence on benzotriazole derivatives that showed potential as anticancer candidates, focusing on the cytotoxicity, mechanisms of action, structure–activity relationship, and methodological rigor of the included studies. Methods: We searched PubMed, Scopus, and Web of Science and included 41 studies in our analysis following the selection process. Additionally, we assessed the risk of bias using the QUIN tool for in vitro and the SYRCLE tool for in vivo studies in order to assess the methodological rigor of the included studies. Results: The benzotriazole derivatives were classified according to their structure in four classes, namely N-derivatives, C-derivatives, fused derivatives, and organometallic compounds. The in vitro results showed that certain derivatives, such as halogen, alkyl-aryl, or natural-base hybrids, can have superior cytotoxicity compared to parent molecules, exerted through multiple mechanisms, such as apoptosis and cell cycle arrest. Additionally, the in vivo analysis highlighted that benzotriazole derivatives can reduce tumor mass in a dose-dependent manner, with only a slight degree of hepatotoxicity reported in one case. However, histopathological data were generally absent or limited and based on a very limited number of in vivo studies. Conclusions: Overall, benzotriazole derivatives remain promising candidates for cancer treatment. However, limited mechanistic and toxicity data, as well as the moderate risk of bias identified across studies, may limit our assessment. Therefore, future studies should employ more rigorous methodologies and explore the underlying anticancer and toxicity mechanisms to fully assess the therapeutic potential of benzotriazole derivatives. Full article

Lung cancer remains a leading cause of cancer mortality worldwide, highlighting the need for novel therapeutics. Here, we designed and synthesized a series of adamantyl-substituted chalcones and identified CA13 as a lead compound with potent and selective antiproliferative activity against non–small cell lung cancer (NSCLC) cells. CA13 triggered both apoptosis and autophagy in H292 cells. Western blotting and confocal imaging confirmed the activation of complete autophagic flux, while inhibition of autophagy markedly enhanced CA13-induced apoptosis, suggesting a cytoprotective role of autophagy. Mechanistically, CA13 activated JNK phosphorylation in a dose- and time-dependent manner, and pharmacological blockade of JNK significantly attenuated apoptotic signaling. In vivo, CA13 effectively suppressed H292 xenograft tumor growth without apparent systemic toxicity. Collectively, these results demonstrate that CA13 exerts its antitumor effects through JNK-dependent apoptosis accompanied by cytoprotective autophagy, providing a promising structural framework for the development of chalcone-based anticancer agents targeting programmed cell death pathways. Full article

Sweet potato leaves (SPL) are increasingly recognized as a significant source of nutritionally and pharmacologically important bioactive compounds. This systematic review critically synthesizes current in vitro, in vivo, and preclinical data to evaluate the cancer preventive properties of SPL, with emphasis on their phytochemical composition, molecular mechanisms, and therapeutic relevance. A comprehensive literature search across major scientific databases (2015–2025), guided by PRISMA methodology, initially identified 29,416 records. After applying pre-specified inclusion and exclusion criteria and screening titles, abstracts, and full-texts, 38 eligible studies were included. The compiled evidence demonstrates that SPL contains high concentrations of phenolic acids, flavonoids, peptides, carotenoids, and dietary fiber, all of which contribute to diverse anticancer activities. Reported mechanisms include apoptosis induction, cell-cycle arrest, limitation of tumor propagation and metastatic activity, regulation of oncogenic pathways (PI3K/Akt, MAPK, NF-κB), modulation of inflammatory mediators, and suppression of angiogenesis. These effects were observed across multiple cancer models, including liver, colon, breast, lung, and prostate cancers. In addition, SPL represents a promising natural source of anticancer agents, significant gaps remain, particularly regarding standardized extraction procedures, phytochemical characterization, bioavailability, and human clinical validation. Overall, this review underscores SPL as a sustainable and underutilized plant resource with potential applications in functional foods, nutraceuticals, and adjunctive cancer therapy, while highlighting the need for mechanistic studies, pharmacokinetic investigations, and well-designed clinical trials to support future translational development. Full article

Background: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with high efficacy in treating patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR-activating mutations. Although osimertinib is a frontline anticancer agent for NSCLC, several patients inevitably develop tumor recurrence caused by osimertinib resistance. The activation of anexelekto (AXL) or fibroblast growth factor receptor 1 (FGFR1) is reported as a major factor driving osimertinib resistance in NSCLC. Thus, targeting AXL and FGFR1 offers the potential to overcome osimertinib resistance. Methods: In this study, we generated osimertinib-resistant cell lines from EGFR-mutant NSCLC cell lines in vitro and investigated the biological significance of AX-0085 on these cell lines by conducting transcriptomic analyses. Results: The expression of several genes associated with MAPK, ERK, and FGF receptor signaling pathways, including AXL, was altered upon AX-0085 treatment of osimertinib-resistant cells. Furthermore, AX-0085 treatment effectively blocked AXL and FGFR1 activation and sensitized osimertinib-resistant cells. Additionally, AX-0085 inhibited AXL and FGFR1-dependent oncogenic events, including cell proliferation, clonogenicity, and migration. Conclusions: The dual inhibition of AXL and FGFR1 by AX-0085 can overcome acquired osimertinib resistance, supporting its potential as a therapeutic strategy for treating patients with osimertinib-resistant tumors. Full article