Search Results (240)

The glycosidic composition of Psolus phantapus was studied for the first time. Two new glycosides, phantapusosides A (1) and B (2), and the known psolusoside P (3) were isolated and their structures were established by analysis of ¹H, ¹³C NMR, 1D TOCSY, and 2D NMR (¹H,¹H COSY, HMBC, HSQC, ROESY), and HR-ESI mass spectra. These compounds are structurally close to those isolated from other representatives of the genus Psolus: P. fabricii, P. peronii and P. chitonoides. These data confirm the chemotaxonomic significance of triterpene glycosides of sea cucumbers, demonstrating that closely related species biosynthesize structurally similar metabolites. The cytotoxic activity of compounds 1 and 2 was studied against four human breast cancer cell lines (MCF-7, T-47D, MDA-MB-231, MDA-MB-468), as well as the non-tumorigenic mammary epithelial cell line MCF-10A and the pancreatic epithelioid carcinoma cell line PANC-1. The glycosides were selectively active against the TNBC cell lines MDA-MB-231 and MDA-MB-468. Notably, both glycosides inhibited the clonogenic potential of TNBC cell lines more significantly than their metabolic activity (MTT assay) and demonstrated a more pronounced colony-inhibiting effect toward the basal-like cell line MDA-MB-468, making this cell line a promising model for future investigation of the antitumor effects of glycosides. Full article

Background: Cancer is a major health concern that significantly impacts the global population. Selective chemotherapeutic delivery is needed to improve the efficacy of cancer therapy while minimizing side effects in healthy cells. This study investigated the potential of gold nanoclusters (AuNCs) functionalized with poly(amidoamine) dendrimers (PAMAM) and folic acid (FA) to selectively deliver doxorubicin (DOX) to cancer cells that express the folate receptor (FR). Methods: AuNC synthesis was confirmed via UV–visible and Fourier transform infrared spectroscopy, nanoparticle tracking analysis, and transmission electron microscopy. Folic acid (FA) was incorporated for cell surface receptor targeting, while the triphenylphosphonium cation (TPP⁺) was added to improve mitochondrial localization. Cytotoxicity (MTT), apoptosis, caspase 3/7, mitopotential, and oxidative stress assays were assessed using human MCF-7 (breast adenocarcinoma), HeLa (cervical carcinoma), Caco-2 (colon adenocarcinoma), MDA-MB-231 (epithelial breast cancer), and the embryonic kidney (HEK293) cells. Results: Favorable DOX loading (>78%), with more than 90% of the drug released at pH 4.5, was achieved. A dose-dependent increase in cytotoxicity was observed, with IC50 values lower in cancer cells than HEK293 cells, indicating selective toxicity and minimal off-target effects. Targeting nanocomplexes produced the best responses in the mitopotential, caspase, and oxidative stress assays in HeLa and MCF-7 cells. Conclusions: The improved cytotoxicity in cancer cells may be due to folate-receptor-mediated cellular uptake, as well as the mitochondrial uptake of TPP⁺ nanocomplexes. This highlighted the potential of the drug–AuNC nanocomplexes to limit systemic side effects, proposing a potential novel strategy for drug delivery to cancer cells. Full article

Background/Objectives: Oral squamous cell carcinoma (OSCC) is a major cause of human cancer. The enzyme, nicotinamide N-methyltransferase (NNMT), is overexpressed in a variety of human cancers, including OSCC. Our objective was to target NNMT with novel inhibitors and determine their anti-cancer efficacy while shedding light on their possible mechanism of action. Methods: We identified two small molecule inhibitors of NNMT (AG-670 and AO-022) based on a pharmacophore of the in silico nicotinamide binding site. These inhibitors were investigated for (i) potency to inhibit the activity of the isolated NNMT enzyme (EC₅₀ values), (ii) cytotoxicity (IC₅₀ values) against the human OSCC cell line, SCC-4, and (iii) ability to affect cellular energy metabolism, as measured by oxygen consumption, in SCC-4 cells (plus dysplastic oral keratinocytes (DOK) cells and breast cancer MCF-7 cells). Immunoblotting was used to determine whether NNMT was expressed in the aforementioned cells. Results: NNMT is expressed in SCC-4 and DOK cells (and primary human oral keratinocytes) but not MCF 7 cells. The NNMT inhibitors inhibit isolated NNMT enzyme activity and were cytotoxic to SCC-4 cells (EC₅₀ and IC₅₀ values in the micromolar range). Sublethal doses of the inhibitors were demonstrated to inhibit in situ mitochondrial oxygen consumption in SCC-4 and DOK cells but not in MCF-7 cells. It was demonstrated that the NNMT inhibitors do not directly inhibit mitochondrial electron transport chain activity. Thus, we deduce that the NNMT inhibitors affect mitochondrial activity indirectly via NNMT. Conclusions: It is concluded that NNMT is a potential drug target for oral cancer. Full article

Epigenetic and stress-response pathways play central roles in cancer progression and represent attractive therapeutic targets. In this study, a series of dipyridothiazine–1,2,3-triazole hybrids bearing p-fluorophenyl and p-trifluoromethylphenyl substituents was synthesized via efficient dipolar cycloaddition reactions. Structural characterization was performed using ¹H, ¹³C, and ¹⁹F NMR spectroscopy and high-resolution mass spectrometry. Anticancer activity was evaluated using WST-1 and MTT assays against human cancer cell lines SNB-19 (glioblastoma), C32 (amelanotic melanoma), A549 (lung carcinoma), and MDA-MB-231 and MCF-7 (breast cancer), as well as normal HFF-1 fibroblasts and HaCaT keratinocytes, with doxorubicin and cisplatin as reference drugs. The hybrids TDT2b and TDT3b containing a p-trifluoromethylphenyl moiety showed the highest cytotoxicity and cancer cell selectivity. RT-qPCR analysis of H3, TP53, CDKN1A, BCL-2, and BAX expression for the lead compound TDT2b revealed modulation of chromatin organization, p53-dependent stress responses, apoptosis, and cell cycle regulation. Molecular docking studies with human histone deacetylase 6 (HDAC6) demonstrated favorable binding of TDT2b and TDT3b, supporting their role as potential epigenetic anticancer agents. Full article

This study reports the exclusive and rapid synthesis of twenty-four derivatives of 1-((mono/bis)trifluoromethyl)phenyl-3-(4-arylthiazol-2-yl)thioureas (series 7, 9 and 11), along with their antimicrobial activities against Candida albicans, Mycobacterium smegmatis and seven additional bacterial strains. The anticancer potential of these compounds was evaluated against various human cancer cell lines, including A549 (lung adenocarcinoma), HeLa (cervical carcinoma), IMR32 (neuroblastoma), MCF-7 (breast adenocarcinoma), HCT116 (colon cancer) and DU145 (prostate cancer). Among these, 1-(3,5-bistrifluoromethylphenyl)-3-(thiazol-2-yl)thiourea (7i) and 1-(4-trifluoromethylphenyl)-3-(4-(3-chlorophenyl)thiazol-2-yl)thiourea (11h) demonstrated significant antimicrobial activity against M. luteus, S. aureus, S. aureus 1 and C. albicans. Additionally, 1-(4-(3-chlorophenyl)thiazol-2-yl)-3-(3-trifluoromethylphenyl)thiourea (9g) and 1-(4-trifluoromethylphenyl)-3-(4-(2-fluorophenyl)thiazol-2-yl)thiourea (11g) showed activity against Mycobacterium smegmatis. The bioassay tests indicated that many of the thiourea derivatives exhibited moderate activity against the A549, HeLa, MCF-7 and HCT116 cancer cell lines. Full article

Background/Objectives: Research on noble metal nanoparticles (NPs) has increased over the past three decades, with advancements in synthesis techniques refining their physicochemical characteristics, including size, shape, and surface chemistry. Bimetallic NPs (BNPs) offer synergistic properties contributed by both metals. Gold (Au) and palladium (Pd) NPs possess low toxicity, high biocompatibility and loading, ease of synthesis and surface modification. Doxorubicin (DOX) and 5-fluorouracil (5-FU) are potent chemotherapeutic drugs but are rapidly metabolised in the body, producing severe side effects, limiting their use. Hence, innovative strategies to mitigate this is needed. Methods: In this study, AuPd NPs in a core-shell formation were chemically synthesized. The AuPd NPs were conjugated to 5-FU and DOX-encapsulated CS complexes and decorated with the targeting moiety transferrin (Tf). Results: Transmission electron microscopy and nanoparticle tracking analysis confirmed that the BNPs were spherical, with an average size of 73.4 nm. Functionalized BNPs were able to encapsulate more than 70% of 5-FU and DOX, resulting in a controlled drug release profile at pH 4.2. Cytotoxicity levels in human cancer cells, HeLa (cervical carcinoma) and MCF-7 (breast adenocarcinoma), as well as in non-cancer HEK293 (embryonic kidney) cells, revealed that the Tf-targeted nanocomplexes were HeLa cell-specific, with no significant cytotoxicity in the HEK293 cells. Tf-mediated cellular uptake was confirmed by receptor competition studies in the HeLa cells. Apoptosis and oxidative stress analysis confirmed cell death by apoptosis, consistent with the action of 5-FU and DOX. Conclusions: This study highlighted the potential of this BNP-nanocomplex as a suitable vehicle for drug delivery. Full article

Harnessing nature’s chemistry, this study explores the enhanced biomedical potential of Terminalia ferdinandiana Exell (Kakadu Plum) by transforming its aqueous leaf and fruit extracts into bio-inspired gold nanoparticles (AuNPs). The synthesis process was optimized by varying the Au³⁺/extract ratio and pH, with nanoparticle formation verified through UV–visible spectrophotometry, TEM, and DLS analyzes. Kakadu Leaf extract–conjugated AuNPs (AuKLs), synthesized at pH 8 with a 1:25 Au³⁺/extract ratio, produced the smallest and most uniform particles (21.1 nm; PDI 0.17). In contrast, fruit extract alone failed to generate stable nanoparticles, highlighting the pivotal role of leaf phytochemicals as natural reducing and stabilizing agents. Biological evaluations revealed that both the crude leaf extract and AuKLs possessed strong antioxidant capacity, while the AuKLs further exhibited selective anticancer activity effectively inhibiting breast cancer (MCF-7) and human cervical carcinoma (HeLa) cell proliferation without harming normal mammalian breast (MCF10A) cells. A combined 2:1 leaf-to-fruit extract formulation yielded well-stabilized AuNPs (AuKPLs) with biomedical properties comparable to AuKLs, though the fruit extract alone contributed minimally to both nanoparticle formation and biological performance. Overall, this study demonstrates that the phytochemical richness of T. ferdinandiana leaves enables the green synthesis of small, stable, and bioactive gold nanoparticles. The resulting nanoconjugates, AuKLs and AuKPLs, hold considerable promise for future pharmacological and therapeutic applications, bridging traditional plant-based medicine with modern nanotechnology. Full article

Background: Both spontaneous and induced 3D spheroid models are among many in vitro models that recapitulate aspects of in vivo cancers. Although numerous studies have described the spatiotemporal relevance of these 3D models, there has been a paucity of studies investigating the signaling pathways that are activated during spheroidgenesis. Methods: Since in vitro 3D spheroidgenesis is thought to reflect at least some of the in vivo aspects of cancer biology (which undoubtedly involve cell adhesion, metabolism, and hypoxia-related pathways) and since we previously investigated these pathways in a model of spontaneous spheroidgenesis, this present study investigates these pathways in a model of induced spheroidgenesis with comparative studies involving a series of well-known E-cadherin-positive (MCF-7, HTB-126, HTB-27) and E-cadherin-negative (MDA-MB-468, MDA-MB-231, BT-549) human breast carcinoma cell lines. Results: Our findings demonstrate that during early induced spheroidgenesis, E-cadherin regulates hypoxia-inducible factor 1-alpha (HIF-1α) predominantly through PI3K/AKT/mTOR signaling and to a lesser extent through Notch1 signaling. Both the knockout of E-cadherin and calpain-mediated E-cadherin proteolysis result in a remarkable reduction in HIF-1α. Conclusions: 3D spheroid models recapitulate, in part, some of the in vivo stages of cancer progression, which include primary tumor clusters, lymphovascular emboli, and micrometastases, the signaling pathways present in these 3D spheroid models likely have relevance in vivo. Full article

Erica spiculifolia Salisb. (Balkan heath) is an evergreen shrub growing in the mountain shrublands of Eastern Europe. E. spiculifolia was used as a diuretic, anti-inflammatory, and antioxidant herbal remedy. The present study aims to conduct an evaluation of the phytochemical composition and antitumor activity of the methanol–aqueous extract from E. spiculifolia aerial parts to explore its potential in cancer treatment. Overall, a total of 54 secondary metabolites, including 28 hydroxybenzoic, hydroxycinnamic acids, and phenolic glycosides, and 10 triterpene acids, together with 17 flavonoids, were identified or annotated in the assayed E. spiculifolia extract using liquid chromatography-high-resolution mass spectrometry. The cytotoxic activity of the extract, alongside gallic, protocatechuic, and oleanolic acids as its constituents, was screened against a panel of malignant human cell lines of different origin (LAMA-84, HL-60, MDA-MB-231, MCF-7, and CASKI). The most prominent antiproliferative effect of the studied extract (with IC₅₀ 16.6 μg/mL), matched with the highest tumor selectivity (SI > 120), was observed in the LAMA-84 myeloid cells. These findings were further supported by gallic and oleanolic acid (IC₅₀ 6.2 and 1.7 μg/mL, respectively), accounting for a more distinct cytotoxicity. The strongest selective antineoplastic activity was achieved towards the triple-negative breast carcinoma cell line MDA-MB-231, with an IC₅₀ of 32.5 μg/mL. This study provided compelling evidence for a wide spectrum of E. spiculifolia antitumor activity, indicating its potential as a natural alternative for future therapeutic applications. Full article

Coumarin derivatives, whether natural or synthetic, have attracted considerable interest from medicinal chemists due to their versatile biological properties. Their appealing pharmacological activities—such as anticancer, anti-inflammatory, neuroprotective, anticoagulant, and antioxidant effects—combined with the ease of their synthesis and the ability to introduce chemical modifications at multiple positions have made them a widely explored class of compounds. In the scientific literature, there are many examples. On the other hand, dithiocarbamates, originally employed as pesticides and fungicides in agriculture, have recently emerged as potential therapeutic agents for the treatment of serious diseases such as cancer and microbial infections. Moreover, dithiocarbamates bearing diverse organic functionalities have demonstrated significant antifungal properties against resistant phytopathogenic fungi, presenting a promising approach to combat the growing global issue of fungal resistance. Dithiocarbamates linked to coumarin derivatives have been shown to exhibit cytotoxic activity against various human cancer cell lines, including MGC-803 (gastric), MCF-7 (breast), PC-3 (prostate), EC-109 (esophageal), H460 (non-small cell lung), HCCLM-7 (hepatocellular carcinoma), HeLa (cervical carcinoma), MDA-MB-435S (mammary adenocarcinoma), SW480 (colon carcinoma), and Hep-2 (laryngeal carcinoma). Numerous studies have revealed that the inclusion of a dithiocarbamate moiety can provide central nervous system (CNS) activity, particularly through inhibitory potency and selectivity toward acetylcholinesterase (AChE) and monoamine oxidases (MAO-A and MAO-B). Recently, it has been reported that coumarin–dithiocarbamate derivatives exhibit α-glucosidase inhibitory effects and also possess promising antimicrobial activity. This study presents an overview of recent progress in the chemistry of coumarin–dithiocarbamate derivatives, with a focus on their biological activity. Previous review papers focused on coumarin derivatives as multitarget compounds for neurodegenerative diseases and described various types of compounds, with dithiocarbamate derivatives representing only a small part of them. Our work deals exclusively with coumarin dithiocarbamates and their biological activity. Full article

The rising incidence of cancer and the limitations of current therapeutic strategies underscore the urgent need to identify novel bioactive compounds for antitumor drug development. Cyanobacteria are widespread Gram-negative, photoautotrophic prokaryotes that have been recognized as an important source of biologically active secondary metabolites with vast potential for application in the fields of pharmaceutics. The aim of the present study was to analyze the phytochemical composition, antioxidant, and antitumor activities of low-temperature (LT) and high-temperature (HT) aqueous extracts of the cyanobacterium Chroococcus sp. R-10. Extracts were prepared and analyzed for phytochemical composition using UPLC-DAD, and antioxidant activity was tested via multiple assays. Antiproliferative effects were evaluated on human tumor cell lines, and the effects on cell cycle progression studied using flow cytometry. Fluorescence microscopy was employed to examine extract-induced cytomorphological changes in the treated cancer cells. UPLC-DAD analyses showed very similar chromatographic profiles of the extracts and identified glycogen as their main constituent. Both extracts displayed concentration-dependent antioxidant activity, with notable radical scavenging and ferric-reducing capacity. LT extract demonstrated higher phenolic content and antioxidant capacity. Both extracts reduced cell viability, particularly in MCF-7 and MDA-MB-231 breast carcinoma cell lines. Flow cytometry and fluorescent microscopy analyses revealed that the suppressed proliferative activity of the cancer cells was associated with a retardation of cell cycle progression and apoptosis induction. This study identifies Chroococcus sp. R-10 as a promising source of phytochemical compounds with pharmaceutical relevance and provides a rationale for further investigations to identify the primary bioactive constituents and elucidate their mechanisms of anticancer action. Full article

Cancer is still the world’s most prevalent cause of death, and the limited efficacy of current treatments highlights the requirement for new therapeutic approaches. In this study, neodymium (Nd)-doped cobalt ferrite (CoFe_2₋zNd_zO₄, z = 0; 0.01; 0.02; 0.03; 0.05; 0.1) nanoparticles (Nd0-Nd5) were synthesized via the combustion method. The structural, morphological, and magnetic properties were characterized using X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), vibrating sample magnetometry (VSM), and scanning transmission electron microscopy (STEM) analysis. The synthesized compounds demonstrated single-phase spinel structures, with morphological differences observed between undoped and Nd-doped samples. The biological activity of the nanoparticles was evaluated on immortalized human keratinocytes (HaCaT) and on cancer cell lines: melanoma (A375), breast adenocarcinoma (MCF-7), and pancreatic carcinoma (PANC-1). The cytotoxic effects of Nd0-Nd5 (50–1000 μg∙mL⁻¹) were assessed through Alamar Blue and lactate dehydrogenase (LDH) release assays. The results indicated a dose-dependent cytotoxic effect in cancer cell lines. Changes in cell morphology, suggesting the induction of the apoptotic processes, were observed through immunofluorescence staining of F-actin and nuclei. These findings highlight the potential of Nd-doped cobalt ferrite nanoparticles as selective anticancer agents, warranting further investigation to fully elucidate their mechanisms of action and therapeutic applicability. Full article

Lopezia racemosa Cav., commonly known as “cancer herb” in indigenous communities, has long been used for its medicinal properties. The biotechnological production of its bioactive compounds through genetic transformation represents a valuable approach for obtaining pharmacologically relevant substances. The initial focus of this study was to identify compounds previously reported in the species; however, phytochemical analysis by HPLC and NMR led to the isolation and identification of two pentacyclic triterpene esters not previously described in L. racemosa: 3-O-[(E)-feruloyl]-maslinic acid (1) and 3-O-[(E)-feruloyl]-corosolic acid (2), identified as constituents of fraction 33. The LRTC3.1 callus line was obtained from hairy roots generated by infecting L. racemosa leaf explants with Agrobacterium rhizogenes strain ATCC15834/pTDT. The crude extract, specific fractions, and the mixture of these compounds demonstrated significant anti-inflammatory and cytotoxic activities. Anti-inflammatory activity was evaluated using the carrageenan-induced mouse paw edema model, where the crude extract achieved 51.02% inhibition of inflammation compared to meloxicam (30.86%). Cytotoxicity was assessed against three human cancer cell lines: breast carcinoma (MCF7), cervical carcinoma (SiHa), and colon carcinoma (HCT-15). Fractions FD (28–29) and 33 exhibited potent cytotoxic effects, with IC₅₀ values of 0.508 and 1.345 µg/mL against SiHa cells, and 0.053 and 2.693 µg/mL against MCF-7 cells, respectively. These findings suggest that transformed L. racemosa cultures represent a promising source of bioactive compounds for potential therapeutic development. Full article

Background: Since breast cancer is a major cause of mortality, investigation of the synergistic effect of Olea europaea L. leaf extract in combination with some cancer medications is important for obtaining cost-effective and high-achieving treatments for breast cancer. This study aims to investigate the potential effects of Olea europaea L. extract in inhibiting breast cancer cell growth and enhancing the efficacy of chemotherapy agents against breast cancer under in vitro conditions. Methods: We conducted an analysis of some minerals and vitamins of three different viscosities (200 V, 300 V, and 400 V as a natural food product) of Olea europaea L. leaf water-based extract (OWE) derived from a natural cold maceration. We investigated the cytotoxic effects of Olea europaea L. extract with different viscosities (200–400 V) and various chemotherapy agents, either alone or in combination, in estrogen receptor-positive MCF-7 human breast carcinoma cells by MTT assay. Olea europaea L. extract treatment of cells resulted in growth inhibition in a dose- and time-dependent manner. Results: The 400 V OWE showed the highest calcium (301 ± 12 mg/100 g), potassium (1744 ± 33 mg/100 g), and vitamin E (0.36 ± 0.01 mg/100 g) amounts. Based on MTT results, combinations of 400V Olea europaea L. extract, which exhibited the strongest inhibitory effect with an IC₅₀ value of 940 µg/mL, and anticancer drugs were next assessed for their synergistic efficacy towards cell growth inhibition. Conclusions: Combinations of the IC₅₀ value of 400 V OWE with docetaxel, paclitaxel, and trastuzumab (1 µg/mL) treatment showed a strong synergistic effect in the growth inhibition of MCF-7 cells. Full article

Background/Objectives: The membrane protein a disintegrin and metalloproteases (ADAMs) are highly expressed in various human carcinomas and play an important role in cancer characteristics. And among these, ADAM32 is highly expressed in hepatoblastoma (HBL) and plays an important role in oncogenic properties. However, the regulatory mechanism has not been determined. Recently, it has been reported that some ADAMs are regulated by HIF, which is an important transcription factor in response to hypoxia. Therefore, we decided to study the regulatory mechanisms of ADAM32 under hypoxic conditions by using HBL, breast, and lung cancer cell lines. Methods/Results: When these cells were exposed to 1% O₂ (hypoxia), it was found that the levels of ADAM32 increased at 48 h in HepG2, MCF7, and MDA-MB-231 but not in HUH-6 or lung cancer lines. However, the promoter activity of the ADAM32 gene in HepG2 remained unchanged under hypoxic conditions, suggesting that the level of ADAM32 in HBL is regulated by factors other than the promoter activity. From the microarray data, we found that the level of IGF2BP2, which is an m⁶A-related molecule, correlated with that of ADAM32, and these levels were decreased by HIF1A knockdown. And IGF2BP2 knockdown decreased the expression of ADAM32 and attenuated the increased expression of ADAM32 under hypoxic conditions. Conclusions: This study demonstrated that the oncogenic gene ADAM32 is regulated by IGF2BP2 and that IGF2BP2 could be a molecular target for HBL anticancer therapy. Full article