Search Results (175)

Objectives: Multiple myeloma and acute myeloid leukemia are severe forms of blood cancer, which lack effective therapies for treatment. In our search for new chemical lead structures from nature, we were investigating the Brazilian medicinal plant arnica-do-cerrado (Lychnophora ericoides). Methods: Repeated chromatography led to the isolation of four flavonoids and three sesquiterpenoids, which were evaluated for their cytostatic and cytotoxic properties against HL-60, MOLM-13, AMO-1, and KMS-12 PE cancer cells as well as the non-malignant HS-5 cell line. Results: Whereas the isolated flavonoids displayed only moderate activity, the three sesquiterpene lactones goyazensolide, centratherin, and lychnopholide exhibited pronounced effects against all four tested cell lines. Goyazensolide was the most effective compound, inhibiting proliferation and metabolic activity with IC₅₀ values between 1.0 and 1.6 µM, as well as 1.0 to 2.0 µM, respectively. Centratherin and lychnopholide were somewhat less active but showed higher selectivity towards malignant cell lines, which was most pronounced for MOLM-13 cells. Conclusion: The results of this study revealed interesting natural products that will be further evaluated for their potential as new lead compounds for the treatment of acute myeloid leukemia and multiple myeloma. Full article

Artemisia serotina Bunge represents one of the endemic Artemisia L. species in flora of Central Asia. There is scant information on the phytochemistry and biological activity of this species. The aim of the present study was to analyze the chemical composition of essential oil from A. serotina (ASEO) growing in south Kazakhstan, together with the determination of its biological activity. ASEO isolation was carried out by hydrodistillation according to the State Pharmacopoeia of the Republic of Kazakhstan. Analysis of GC/MS data revealed that the most characteristic components of ASEO were irregular monoterpenes from three families: santolinane, artemisane, and lavandulane. The major compound was santolina alcohol (34.6%). Antimicrobial activity was studied against the reference bacterial and fungal strains using the recommended methods, allowing for an estimation of MIC (minimum inhibitory concentration). ASEO was most effective against Candida albicans (MIC = 2 mg/mL), exerting fungicidal activity. Thw MIC for bacterial species was higher, i.e., 4–16 mg/mL. Antiviral activity was tested against Coxsackievirus B3 (CVB3) and Human Herpesvirus type 1 (HHV-1) propagated in VERO cells. No antiviral effect against either virus was found at an ASEO concentration of 0.25 mg/mL, but a noticeable decrease in the intensity of HHV-1-related cytopathic effects was observed. Anticancer activity studies included several cancer cell lines. Cytotoxicity, cell cycle, thiol levels, and cell vitality were analyzed. Among the cancer cell lines tested, the breast cancer T47-D cell line exhibited the highest sensitivity to ASEO (IC₅₀ = 40.81 ± 4.21 µg/mL at 24 h; IC₅₀ = 33.17 ± 2.11 µg/mL at 48 h). The anticancer effect was suggested to be mainly due to the induction of cytostatic effects, accompanied by a disturbance of the intracellular redox balance. The obtained data provide novel information on the unique chemical composition of ASEO from south Kazakhstan, representing a new chemotype. Its bioactivity, including promising antifungal and anticancer properties, was demonstrated for the first time. Full article

Natural compounds remain a valuable source of anticancer agents due to their structural diversity and multi-targeted mechanisms of action. Roburic acid (RA), a tetracyclic triterpenoid, has been identified as a substance capable of inhibiting key NF-κB and MAPK signaling pathways through direct interaction with TNF-α, as well as preventing the production of inflammatory mediators and cancer progression. In this study, we evaluated the biological activity of RA against a panel of human cancer cell lines—DLD-1, HT-29, and HCT-116 (colorectal), PC-3 (prostate), and BxPC-3 (pancreatic)—as well as two non-malignant lines: WI-38 (fibroblasts) and CCD-841 CoN (colon epithelium). RA exhibited a concentration-dependent inhibitory effect on cancer cell metabolic activity, with colorectal cancer cells showing relatively higher sensitivity, particularly at shorter incubation times. To distinguish between cytotoxic and cytostatic effects, we performed trypan blue exclusion combined with a cell density assessment, clonogenic assay, and BrdU incorporation assay. The results from these complementary assays confirmed that RA acts primarily through an antiproliferative mechanism rather than by inducing cytotoxicity. In addition, NF-κB reporter assays demonstrated that RA attenuates TNF-α-induced transcriptional activation at higher concentrations, supporting its proposed anti-inflammatory properties and potential to modulate pro-tumorigenic signaling. Finally, our in silico studies predicted that RA may interact with proteins such as CAII, CES1, EGFR, and PLA2G2A, implicating it in the modulation of pathways related to proliferation and cell survival. Collectively, these findings suggest that RA may serve as a promising scaffold for the development of future anticancer agents, particularly in the context of colorectal cancer. Full article

The development of resistance to standard cytostatics, such as 5-fluorouracil (5-FU), significantly limits the efficacy of colon cancer therapy, prompting the search for novel anticancer agents, particularly among natural compounds. This study evaluated the anticancer effects of isorhamnetin, a plant-derived flavonol, and its ability to modulate the expression of drug-resistance-related biomarkers in SW-480 and HT-29 colon cancer cells, with a focus on ATP-binding cassette (ABC) transporters. Isorhamnetin demonstrated strong cytotoxic and proapoptotic activity on both cell lines, while showing lower toxicity toward normal HaCaT cells. In addition to suppressing the mRNA expression of drug-metabolizing enzymes (CYP1A1 and CYP1B1), isorhamnetin significantly reduced the mRNA levels of multidrug resistance-associated proteins 1 and 5 (MRP1 and MRP5), as well as the P-glycoprotein (P-gp) level in SW-480 and HT-29 cells. Molecular docking analysis revealed a high binding affinity of isorhamnetin to CYP1A1, CYP1B1, P-gp, MRP1, MRP5, and glutathione S-transferase (GST) proteins, with stronger interactions than those observed for 5-FU, suggesting potential interference with their function. These results provide a solid basis for future investigations to confirm the therapeutic potential of isorhamnetin as a modulator of drug resistance in colon cancer cells. Full article

Background/Objectives: Cancer remains a major global health challenge, driving the search for novel chemotherapeutic agents. This study aimed to evaluate the structural and biological properties of a series of Pd(II) complexes containing triphenylphosphine and thiosemicarbazone ligands, in order to assess their potential as anticancer agents. Methods: Six Pd(II) complexes with the general formula [PdCl(PPh₃)(TSC)] were synthesized and fully characterized by NMR (¹H, ¹³C, ³¹P), FTIR, mass spectrometry, and X-ray diffraction. Their cytotoxic effects were investigated through in vitro assays using 2D and 3D cancer cell models, including clonogenic, wound healing, cell cycle, and apoptosis assays via flow cytometry. Results: Complexes from the B family demonstrated significantly higher cytotoxicity than those from the C family, particularly against ovarian (IC₅₀ < 1 µM) and breast (IC₅₀~2 µM) cancer cell lines. These compounds exhibited superior potency and selectivity compared to cisplatin, with high selectivity indices toward non-tumor cells. Mechanistic studies revealed both cytotoxic and cytostatic effects depending on structural variations, with apoptosis identified as the primary mechanism of cell death. PdB1, in particular, induced a marked increase in late apoptotic populations and maintained its cytotoxic activity in 3D spheroid models by promoting disintegration, loss of cell adhesion, and nuclear fragmentation. Conclusions: The findings underscore the therapeutic promise of Pd(II) complexes, especially PdB1, as potent and selective antineoplastic agents capable of acting effectively in complex tumor environments and potentially overcoming chemoresistance. Full article

Essential oils (EOs) of three native species Baccharis uncinella, B. retusa and B. calvescens, obtained through hydrodistillation, were analyzed by GC-MS and GC-FID for seasonality, and the antimicrobial and anti-proliferative activities were evaluated. EO of B. calvescens and B. uncinella consisted mainly of oxygenated sesquiterpenes, while in the EO of B. retusa, monoterpene hydrocarbons were predominant. The highest antimicrobial activity was observed for spring B. uncinella EO against S. aureus, C. albicans and summer B. uncinella EO against C. albicans and B. subtilis. Essential oils of B. calvescens showed more effective anti-proliferative activity than B. retusa EO and B. uncinella EO. This is the first study of the EO of B. retusa, and it was demonstrated that the majority composition was different in all seasons of the year, justifying the importance of the seasonal study. Furthermore, the summer and spring EO showed potent cytostatic effects against the K562 and OVCAR-03 cell lines, respectively. For each species, PCA differentiated the EO chemical composition seasonally. PCA of all samples distinguished the three species. This study underscores the importance of assessing seasonal variation in the chemical composition and biological activities of essential oils, highlighting the potential of compounds spathulenol, caryophyllene oxide, limonene and α-pinene for achieving the desired product properties. Full article

In the search for new selective inhibitors of human carbonic anhydrase (hCA), particularly the cancer-associated isoforms hCA IX and hCA XII, a series of 4-substituted pyridine-3-sulfonamides was synthesized using the “click” CuAAC reaction, proven by X-ray crystallography, and evaluated for their inhibitory activity against hCA I, hCA II, hCA IX, and hCA XII. Additional molecular docking studies and cytostatic activity assays on three cancer cell lines were conducted. The compounds exhibited a broad range of inhibitory activity, with K_I reaching 271 nM for hCA II, 137 nM for hCA IX, and 91 nM for hCA XII. Notably, compound 4 demonstrated up to 5.9-fold selectivity toward the cancer-associated hCA IX over the ubiquitous hCA II, while compound 6 exhibited a remarkable 23.3-fold selectivity between transmembrane isoforms hCA IX and hCA XII. Molecular docking studies have shown the possibility of selective interaction with the hydrophilic or lipophilic half of the active site, what results from the adjacent (3,4) position of the “tail” in relation to the sulfonamide group. Full article

Mesenchymal stromal cells (MSCs) influence tumor biology and immunology by releasing cytokines, chemokines and growth factors. Currently, cisplatin is an integral part of drug-based tumor therapy, for example, in head and neck squamous cell carcinoma (HNSCC). Cisplatin treatment induces apoptosis as a primary mechanism of action; however, additional immunomodulatory effects of cisplatin are gaining interest. The aim of this study is to evaluate the possible immunomodulatory effects of cisplatin in human MSCs (hMSCs). The MSCs, obtained from human bone marrow, were characterized by analyzing plastic adherence, typical surface features, and ability to differentiate. Toxicity analysis of cisplatin’s effects on primary MSCs, including the determination of a subtoxic concentration, was performed using the MTT assay. Enzyme-linked immunosorbent assays (ELISA) and a quantitative real-time polymerase chain reaction (qRT-PCR) were used to identify potentially immunomodulatory factors. Additionally, a scratch assay was performed to evaluate cell migration. First, subtoxic cisplatin concentrations were determined. A significantly reduced protein expression of indoleamine 2,3-dioxygenase 1 (IDO1) in MSCs under the influence of subtoxic cisplatin concentrations was demonstrated. Similarly, IL-6 protein expression was qualitatively reduced at subtoxic concentrations, although without statistical significance. At the mRNA level, qRT-PCR showed a non-significant, cisplatin concentration-dependent reduction in the expression of both IL-6 and IDO1. The scratch assay showed no statistically significant influence on migration after cisplatin treatment. In MSCs, there is tendency to a decrease in IL-6 and IDO1 at both protein and mRNA level after cisplatin exposure. These effects are congruent with each other and dose-dependent. This indicates that cisplatin not only acts via the known cytotoxic effect, but may induce a reduction in tumor-supporting proteins, like IL-6 and IDO1, by MSCs in the tumor microenvironment at subtoxic concentrations. Traditional cytostatic compounds, which can favorably modulate the immune system in the tumor microenvironment, may open new avenues to explore treatment strategies specifically targeting immunomodulation. Overall, the results indicate beneficial immunomodulation by cisplatin. Full article

Germacranes are a type of sesquiterpene lactones with anti-inflammatory and cytotoxic properties against cancer cell lines. In this in vitro study, erioflorin and erioflorin acetate were isolated and purified from the leaves of Podanthus mitiqui Lindl (Mitique or Mitriu), a shrub endemic to Chile and traditionally used in Mapuche medicine to treat urinary and digestive disorders. Their effects on advanced prostate cancer cell lines (DU-145 and 22Rv1) were evaluated. Cytotoxicity was assessed using real-time cell death and clonogenic assays. Apoptosis was determined by measuring reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), and apoptotic cell percentage through flow cytometry. Gene expression of BAX and BCL-2 was analyzed via RT-qPCR, while NF-κB activation was studied in DU-145 cells and human monocytic NF-κB reporter assays using LPS stimulation and alkaline phosphatase activity quantification. Erioflorin acetate exhibited the highest cytotoxicity, with IC₅₀ values of 35.1 µM (22Rv1) and 27.3 µM (DU-145), compared to erioflorin, which had IC₅₀ values of 50.3 µM and 56.5 µM, respectively. Both compounds increased ROS levels, reduced ΔΨm, and induced apoptosis. RT-qPCR analysis revealed that erioflorin elevated the BAX/BCL-2 ratio, and both compounds inhibited NF-κB activation by preventing IκBα phosphorylation. In conclusion, the findings demonstrate that erioflorin and erioflorin acetate exert significant in vitro cytotoxic and cytostatic effects on prostate cancer cells, supporting their potential as natural candidates for prostate cancer therapy. Full article

The aim of this study was to synthesize new racemic and optically pure aryl-substituted purine bioisosteres using ultrasound-assisted Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition. Regioselective synthesis of α-azido alcohols was applied to afford heterocycles with a 2-hydroxyeth-1-yl linker. Catalytic asymmetric synthesis using halohydrin dehalogenase in the ring-opening of epoxides gave enantioenriched azido alcohols, which subsequently afforded R- and S-enantiomers of purine and pyrrolo[2,3-d]pyrimidines with a 1-hydroxyeth-2-yl linker. The newly synthesized compounds were evaluated in vitro for their antiproliferative activity against four malignant tumor cell lines. The influence of regioisomerism and the stereochemistry of the hydroxyethyl group, as well as a N-heterocyclic scaffold linked to the aryl moiety on cytostatic activity was evaluated. Of all the compounds tested, purine 40a and pyrrolo[2,3-d]pyrimidine 45a derivatives with p-trifluoromethyl-substituted aryl connected to 1,2,3-triazole via a 2-hydroxyeth-1-yl spacer showed promising submicromolar antiproliferative activity. In addition, compound 45a exhibited selectivity towards the tumor cell line, with a selectivity index (SI) of 40, moderate clearance, and good membrane permeability. Full article

Cytotoxic antibiotics (CA) present a pressing environmental concern due to their persistence and potential adverse effects on ecosystems and human health. Conventional wastewater treatment methods often fail to effectively remove these compounds, making it necessary to explore advanced oxidation processes (AOPs) as promising alternatives. This review aims to synthesize global data on the dosages and environmental concentrations of common CA in diverse water sources, while evaluating the efficacy of AOPs in degrading these contaminants. Various AOPs, including photocatalysis, ozonation, and Fenton-like processes, or their combination, are discussed, highlighting their mechanisms and efficiency in eliminating cytotoxic antibiotics from aqueous environments. In addition, information about the degradation by-products is provided. The rising consumption of cytotoxic drugs underscores the need for this up-to-date review, as diseases were CA are used as treatment, show increasing numbers. By consolidating recent developments and outlining challenges and opportunities, this review serves as a valuable resource for researchers, engineers, and policymakers involved in mitigating the environmental impact of cytotoxic antibiotics through AOPs. Full article

Targeting the tumor microenvironment (TME) is an attractive strategy for developing new drugs with anticancer activity against triple-negative breast cancer (TNBC). Interleukins (ILs) are key players in the TME cytokine network promoting cancer progression. Recent studies have highlighted the involvement of IL-20 receptor subunit alpha (IL-20RA) signalling in several cancers, including BC, in which IL-20RA is highly expressed, correlating with poor prognosis and influencing tumoral characteristics such as proliferation, cell death, invasiveness, and TME activity. Therefore, elucidating the role of the IL-20RA signalling pathway could form the basis for developing new therapeutic strategies. This study aimed to identify selective bioactive ligands able to affect IL-20RA activity. Virtual screening of over 310,000 compounds from both the DrugBank and ZINC15 databases identified four potential hit compounds tested for their anticancer activity against TNBC in vitro cell lines. Notably, Ritonavir, a well-known Human Immunodeficiency Virus Type 1 (HIV-1) protease inhibitor, significantly inhibited cell proliferation (about 40% at 50 µM, p < 0.001). IL-20 preincubation counteracted Ritonavir’s cytostatic effect while IL-20RA knockdown restored proliferation in Ritonavir-treated TNBC cells. In conclusion, these findings demonstrated that Ritonavir reduced TNBC cell proliferation through IL-20RA activity modulation, suggesting its potential repurposing as a therapeutic agent for TNBC management. Full article

Two natural ent-kaurene diterpenoids, ent-15α-angeloyloxykaur-16-en-3β-ol (7) and ent-15α-angeloyloxykaur-16-en-3β,9-diol (8), were extracted from the aerial parts of Distichoselinum tenuifolium, and six new derivatives were synthesised from compound (7). The antitumour properties of these natural and derivative ent-kaurenes (2, 7, 9–13) were evaluated in three cancer cell lines: HT29 (colon cancer), HepG2 (hepatocellular carcinoma), and B16-F10 (murine melanoma). Among them, the synthesised ent-kaurene (13) containing an exomethylene–cyclopentanone moiety showed the strongest antiproliferative effects in all cell lines tested, with significantly lower IC₅₀ values around 2.5 μM. Compounds 13 and 12, together with their precursor (7), were selected for further comparative cytometric and microscopic analyses. Cell cycle studies revealed that derivatives 12 and 13 exhibited promising cytostatic activity by inducing selective G2/M phase arrest, particularly effective in HT29 and HepG2 cells. Conversely, precursor (7) showed no significant effect on B16-F10 cell cycle distribution. The Annexin V-FITC/PI double staining assay confirmed the robust apoptotic effects of compounds (7), 12 and 13, with compound 13 inducing up to 99% total apoptosis and exhibiting significant apoptotic activity in all cell lines tested. These apoptotic effects were closely linked to mitochondrial dysfunction, as evidenced by a marked loss of mitochondrial membrane potential and reduced Rh123 fluorescence in treated cells, thereby activating the intrinsic apoptotic pathway. These findings highlight the critical role of mitochondrial disruption in the cytotoxic mechanisms of these ent-kaurenes and underscore their potential as promising anticancer agents. Full article

Background/Objectives: Glioblastoma (GBM) is the most aggressive type of brain tumor in adults. Currently, the only treatments available are surgery, radiotherapy, and chemotherapy based on temozolomide (TMZ); however, the prognosis is dismal. Several natural substances are under investigation for cancer treatment. 8α-O-(3,4-dihydroxy-2-methylenebutanoyloxy) dehydromelitensine (Isocnicin) is a natural compound derived from Centaurea species and was found to exhibit cytostatic/cytotoxic effect against different cell lines. In this study, we investigated the anti-glioma effects of isocnicin in U87 and T98 glioblastoma cell lines, as well as the effects of combined treatment with radiotherapy. Methods: Cell viability was evaluated with the trypan blue exclusion assay, cell cycle distribution was examined using flow cytometry, and the effects of the combination treatment were analyzed with CompuSyn software(1.0). Results: The result showed that isocnicin significantly reduced cell viability in U87 and T98 cell lines in a dose-dependent manner and IC₅₀ values were calculated. Administration of isocnicin alone induced both S and G2/M cell cycle arrest in U87 and T98 cells in a dose-dependent manner. Moreover, when cells were treated with increasing concentrations of isocnicin, followed by 2 or 4 Gy of radiation, the percentage distribution of the cells in the G2/M phase was increased considerably in both U87 and T98 cell lines. Conclusions: Here, we show for the first time that co-treatment of isocnicin with radiation exerts a synergistic antiproliferative effect in glioblastoma cell lines. Natural compounds are promising for glioblastoma treatment. Further studies will be necessary to unravel isocnicin’s mechanism of action and its synergistic effect with radiation on glioblastoma treatment. Full article

Despite significant efforts, cancer remains the second leading cause of mortality worldwide. The medicinal plant Nepeta nuda L. represents a valuable source of biologically active compounds with pharmacological activities including antioxidant, anti-inflammatory, antimicrobial, and antiviral. This study aimed to assess the antiproliferative potential and mechanisms of action of aqueous extract from the leaves of wild-grown N. nuda. Cancer cell lines, MDA-MB-231, MCF7 (breast), HT29, Colon 26 (colon), and HepG2 (liver cancer), and a non-cancerous skin cell line, BJ, were assessed for antiproliferative activity by MTT assay and observation of cell morphological alterations. The cancer cell line that was most sensitive to the extract was further studied for apoptotic alterations by Annexin V/propidium iodide staining, colony-forming assay, and qRT-PCR analysis. The results revealed that the plant extract inhibited the proliferation of all investigated cancer cell lines with the strongest cytostatic effect on Colon 26 cells with a half maximal inhibitory concentration (IC₅₀) value of 380.2 μg/mL and a selectivity index (SI) of 3.5. The extract significantly inhibited the ability of cells to form colonies, exhibited considerable proapoptotic potential involving the participation of the CASP8 gene, and increased the expression levels of ATG3 and the BECN1 gene, which suggests a role of autophagic cell death in the antitumor action. Full article