Search Results (170)

Background: Liposomes and, more recently, structured nanolipid particles have demonstrated effectiveness as carriers for delivering hydrophilic or lipophilic anticancer agents, enhancing their biocompatibility, bioavailability, and sustained release to target cells. Objective: Herein, four doxorubicin formulations—comprising either the acidic or neutral form—were encapsulated into liposomes (Lipo) or nanostructured lipid carriers (NLCs) and characterized in terms of size, entrapment efficiency, morphology, and effects on two cancer cell lines (melanoma B16-F10 and breast carcinoma Walker 256 cells). Methods and Results: While liposomal formulations containing acidic doxorubicin displayed IC₅₀ values ranging from 1.33 to 0.37 µM, NLC-based formulations, particularly NLC-Doxo@Ac, demonstrated enhanced cytotoxicity with IC₅₀ values as low as 0.58 µM. Neutral Doxorubicin demonstrated lower cytotoxicity in both the nanoformulations and cell lines. Differences were also observed in their internalization patterns, cell-cycle impact, and apoptotic/necrotic effects. Compared to liposomes, NLCs exhibited distinct internalization patterns and induced stronger cell-cycle arrest and necrosis, especially in melanoma cells. Notably, NLC-Doxo@Ac outperformed liposomal counterparts in melanoma cells, while liposomal formulations showed slightly higher efficacy in Walker cells. Early and late apoptosis were more pronounced in Walker cells, whereas necrosis was more prominent in melanoma B16-F10 cells, particularly with the nanolipid formulations. Conclusions: These results correlated positively with cell-cycle measurements, highlighting the potential of NLCs as an alternative to liposomes for the delivery of neutral or acidic doxorubicin, particularly in tumor types that respond poorly to conventional formulations. Full article

Tetracyclic bis-piperidine alkaloids (TcBPAs) are structurally complex natural products primarily isolated from marine sponges of the order Haplosclerida. Distinguished by their intricate architecture, TcBPAs feature two central piperidine units linked by dual macrocyclic rings. These unique structural motifs contribute significantly to their biological activities. For example, TcBPAs exhibit antiproliferative activities at low micromolar concentrations across various cancer cell lines, including leukemia, melanoma, breast, colon, fibrosarcoma, and glioblastoma. Despite this promising therapeutic profile, the structural intricacy of TcBPAs has posed considerable challenges to the development of efficient synthetic methodologies, thereby limiting comprehensive exploration and potential clinical advancement. This review highlights recent progress and persisting challenges in the synthesis, structural analysis, and biological evaluation of TcBPAs, underscoring their therapeutic potential in anticancer drug discovery. Full article

Parietaria judaica L. (alfavaca-de-cobra) was investigated as a potential source of anticancer compounds. Leaf extracts obtained using solvents of different polarities were evaluated for their phytochemical profiles and cytotoxic activities against a panel of human cancer cell lines (glioblastoma LN-229, lung NCI-H1563, breast MDA-MB-231, liver HepG2, renal 769-P, cervical HeLa, and melanoma A-375) and a noncancerous HEK-293 cell line. LC-ESI-MS/MS analysis confirmed that the extracts are rich in polyphenols, including phenolic acids and flavonoids. Cytotoxicity was assessed via MTT and SRB assays, demonstrating dose-dependent antiproliferative effects. Among the extracts, the ethanolic fraction (PJ-E) exhibited the strongest cytotoxicity, with an IC₅₀ of 11.82 µg/mL against HeLa cells, while displaying a significantly higher IC₅₀ (139.42 µg/mL) against HEK-293, indicating tumor selectivity. The water extract (PJ-W) showed selective activity against lung cancer cells (IC₅₀ = 87.69 µg/mL), with minimal toxicity toward normal cells. The methanol/acetone extract (PJ-M) displayed intermediate activity, whereas the hexane extract (PJ-H) was the least effective. These findings highlight P. judaica, particularly its ethanolic extract, as a promising source of natural anticancer agents. Further research focusing on the isolation of active constituents, formulation development, and in vivo validation is warranted to support its therapeutic potential. Full article

Autophagy plays a central role in cellular degradation and recycling pathways involving the formation of autophagosomes from cellular components. The Atg8 protein family, particularly LC3, is essential to this process, and dysregulation has been implicated in many diseases (including cancer). Furthermore, therapeutic strategies targeting Atg8 proteins like LC3 can be advanced by exploiting the expanding knowledge of the “LC3 interacting region” (LIR) domain to develop inhibitory ligands. Here, we report a computational approach to design novel peptides that inhibit LC3B. The LIR domain of a known LC3B binder (the FYCO1 peptide) was used as a starting point to design new peptides with unnatural amino acids and conformational restraints. Accomplishing molecular dynamics simulations and binding free energy calculations on the complex of peptide–LC3B, new promising FYCO1 analogs were selected. These peptides were synthesized and investigated by biophysical and biological experiments. Their ability to affect cellular viability was determined in different cancer cell lines (prostate cancer, breast cancer, lung cancer, and melanoma). In addition, the ability to inhibit autophagy and enhance the apoptotic activity of Docetaxel was evaluated in PC-3 prostate cancer cells. In conclusion, this research presents a rational approach to designing and developing LC3B inhibitors based on the FYCO1-LIR domain. The designed peptides hold promise as potential therapeutic agents for cancer and as tools for further elucidating the role of LC3B in autophagy. Full article

In this study, praseodymium-doped cobalt ferrite nanoparticles (CoFe_2−yPr_yO₄, y = 0–0.2) were synthesized via sol-gel auto-combustion and systematically characterized to assess their structural, morphological, magnetic, and biological properties. X-ray diffraction (XRD) confirmed single-phase cubic cobalt ferrite formation for samples with y ≤ 0.05 and the emergence of a secondary orthorhombic PrFeO₃ phase at higher dopant concentrations. FTIR spectroscopy identified characteristic metal–oxygen vibrations and revealed a progressive shift of absorption bands with increasing praseodymium (Pr) content. Vibrating sample magnetometry (VSM) demonstrated a gradual decline in saturation (Ms) and remanent (Mr) magnetization with Pr doping, an effect further intensified by cyclodextrin surface coating. TEM analyses revealed a particle size increase correlated with dopant level, while SEM images displayed a porous morphology typical of combustion-synthesized ferrites. In vitro cell viability assays showed minimal toxicity in normal human keratinocytes (HaCaT), while significant antiproliferative activity was observed against human cancer cell lines A375 (melanoma), MCF-7 (breast adenocarcinoma), and HT-29 (colorectal adenocarcinoma), particularly in Pr 6-CD and Pr 7-CD samples. These findings suggest that Pr substitution and cyclodextrin coating can effectively modulate the physicochemical and anticancer properties of cobalt ferrite nanoparticles, making them promising candidates for future biomedical applications. Full article

The dinuclear platinum(IV) compound {Pt(CH₃)₃}₂(μ-I)₂(μ-adenine) (abbreviated Pt₂ad), obtained by treating cubic [Pt^IV(CH₃)₃(μ₃-I)]₄ with two equivalents of adenine, was isolated and structurally characterized by single crystal X-ray diffraction. The National Cancer Institute Developmental Therapeutics Program’s in vitro sulforhodamine B assays showed Pt₂ad to be particularly cytotoxic against the central nervous system cancer cell line SF-539, and the human renal carcinoma cell line RXF-393. Furthermore, Pt₂ad displayed some degree of cytotoxicity against non-small cell lung cancer (NCI-H522), colon cancer (HCC-2998, HCT-116, HT29, and SW-620), melanoma (LOX-IMVI, Malme-3M, M14, MDA-MB-435, SK-MEL-28, and UACC-62), ovarian cancer (OVCAR-5), renal carcinoma (A498), and triple negative breast cancer (BT-549, MDA-MB-231, and MDA-MB-468) cells. Although anticancer studies involving some adenine platinum(II) compounds have been reported, this study marks the first assessment of the anticancer activity of an adenine platinum(IV) complex. Full article

Changes in skin pigmentation, like hyperpigmentation or moles, can affect appearance and social life. Unlike locally containable moles, malignant melanomas are aggressive and can spread rapidly, disproportionately affecting younger individuals with a high potential for metastasis. Research has shown that the peroxisome proliferator-activated receptor gamma (PPAR-γ) and its ligands exhibit protective effects against melanoma. As a transcription factor, PPAR-γ is crucial in functions like fatty acid storage and glucose metabolism. Activation of PPAR-γ promotes lipid uptake and enhances sensitivity to insulin. In many cases, it also inhibits the growth of cancer cell lines, like breast, gastric, lung, and prostate cancer. In melanoma, PPAR-γ regulates cell proliferation, differentiation, apoptosis, and survival. During tumorigenesis, it controls metabolic changes and the immunogenicity of stromal cells. PPAR-γ agonists can target hypoxia-induced angiogenesis in tumor therapy, but their effects on tumors can be suppressive or promotional, depending on the tumor environment. Published data show that PPAR-γ-targeting agents can be effective in specific groups of patients, but further studies are needed to understand lesser-known biological effects of PPAR-γ and address the existing safety concerns. This review provides a summary of the current understanding of PPAR-γ and its involvement in melanoma. Full article

Nanotechnology has revolutionized cancer therapy by enabling targeted drug delivery and overcoming limitations associated with conventional chemotherapy. In this study, we explored the anticancer potential of gold–iron oxide (Au-Fe₃O₄@PEG) nanourchins (NUs), a class of nanoparticles with unique shape, surface features, and plasmonic properties. We tested NUs on several cancer cell lines, including A375 (melanoma), MCF7 (breast), A549 (lung), and MIA PaCa-2 (pancreatic), and observed significant dose-dependent cytotoxicity, with A549 cells exhibiting the highest resistance. Our findings also demonstrate that NUs induce oxidative stress, disrupt mitochondrial function, and activate autophagic and paraptotic cell death pathways in A549 lung cancer cells. Additionally, we explored the potential of NUs to enhance the efficacy of platinum-based chemotherapy, specifically cisplatin, in A549. The results provide valuable insights into the therapeutic potential of NUs in the context of cancer treatment, particularly for overcoming drug resistance and enhancing the effectiveness of conventional chemotherapy. Full article

A series of novel hydrazones bearing diphenylamine and 5-oxopyrrolidine moieties, along with benzene and naphthalene rings substituted with hydroxy, alkoxy, or carboxylic groups, were synthesized. Their anticancer activity was evaluated in vitro using both 2D (MTT and ‘wound healing’ assays) and 3D (cell spheroid) models against human melanoma IGR39 cells, the triple-negative breast cancer cell line MDA-MB-231, and pancreatic carcinoma Panc-1 cell line. Compounds 8 (2-hydroxybenzylidene derivative) and 12 (2-hydroxynaphthalenylmethylene derivative) demonstrated the highest cytotoxicity in both 2D and 3D assays, while compounds 4 (2,5-dimethoxybenzylidene derivative) and 6 (2,4,6-trimethoxybenzylidene derivative) were most effective at inhibiting cell migration. Notably, all compounds exhibited lower activity against the Panc-1 cancer cell line in a cell monolayer, but the effects on spheroid cell viability in 3D models were comparable across all tested cancer cell lines. Molecular docking studies of the most active hydrazones suggested that these compounds may act as multikinase inhibitors. In particular, 2-hydroxynaphthalenylmethylene derivative 12 showed high binding affinity values (−11.174 and −11.471 kcal/mol) to the active sites of two key protein kinases—a non-receptor TK (SCR) and STPK (BRAF)—simultaneously. Full article

This study investigated the antiproliferative activity of three classes of benzo[f]pyrrolo[1,2-a]quinoline azatetracyclic derivatives. All compounds were screened against 60 cancer cell lines at a single dose of 10 μM. When we compared the activity of the three classes of azatetracyclic derivatives (azide, monobrominated and dibrominated), we found that the dibrominated compounds were less active, while the azides were the most active molecules. Compounds 3b and 5a, showing the best growth inhibition profile of all the drugs evaluated, were selected for the second stage of a full five-dose testing. According to the results of the in vitro screening, compounds 3b and 5a exhibit good to moderate anticancer activity (in micromolar range) against all nine cancer sub-panels, with compound 5a being more selective than compound 3b. Both compounds presented better activity than phenstatin on T–47D breast cancer cells, with compound 3b also being more active on SK–MEL–28 melanoma cells, while compound 5a was more active than phenstatin on COLO 205 colon cancer cells. As for the probable mechanism of action, the benzoquinoline derivatives could act as PI5P4Kα and PI5P4Kβ inhibitors or topoisomerase II inhibitors. Full article

Biologically active compounds of natural origin, such as betulin, are a source of obtaining new medicinal substances. The presence of chemically active hydroxyl groups in the betulin structure at C-3 and C-28 positions enables esterification with dicarboxylic acid anhydrides or carboxylic acids. As a result of a four-step synthesis, difunctional betulin derivatives were obtained, which were evaluated for their antiproliferative activity against the following human cell lines: leukemia (MV4-11), (A549), breast cancer (MCF-7), prostate adenocarcinoma (PC-3), colon cancer (HCT116), pancreatic cancer (MiaPaca-2), and melanoma (Hs294T). The target 3-carboxyacyl-28-alkynyloyl betulin derivatives showed significant antiproliferative activity against MV4-11 cells. For 3-carboxyacylbetulins and their selected alkynyl derivatives, studies to investigate the effect on the cell cycle and apoptosis process, as well as drug similarity analysis, were performed. Full article

Background/Objectives: Natural cytokinins are a promising group of anti-tumor agents. In this work, we hypothesized that modification of the ethylenediurea moiety with alkyl and oxygen-containing groups could be a way to enhance the anti-proliferative properties of the molecule. Methods: Ten new analogs of ethylenediurea with these substitutions were tested for anti-proliferative activity in the human cancer cell lines MDA-MB-231 (breast cancer), A-375 (melanoma), and U-87 MG (glioblastoma) during 72 h of incubation using resazurin test and evaluated the substances receptor using molecular docking. Results: The compound with the carbamate link and ethylene substituent on the phenyl ring inhibited proliferation in these models by 70–90% without cytotoxic effects. The compound did not affect the viability of the immortalized fibroblast cell line Bj-5ta. The compound was also able to enhance the action of doxorubicin and temozolomide by about 20%. According to the molecular modeling data, the probable receptor target for the synthesized compound was the A2AR adenosine receptor. Conclusions: The results obtained on the ethylenediurea analogs with ethyl substituent in the aromatic ring are promising for the development of novel anticancer therapeutics. Full article

Background/Objectives: The synthesis of (E)-1-(1,3-diphenylallyl)-1H-1,2,4-triazoles and related compounds as anti-mitotic agents with activity in breast cancer was investigated. These compounds were designed as hybrids of the microtubule-targeting chalcones, indanones, and the aromatase inhibitor letrozole. Methods: A panel of 29 compounds was synthesized and examined by a preliminary screening in estrogen receptor (ER) and progesterone receptor (PR)-positive MCF-7 breast cancer cells together with cell cycle analysis and tubulin polymerization inhibition. Results: (E)-5-(3-(1H-1,2,4-triazol-1-yl)-3-(3,4,5-trimethoxyphenyl)prop-1-en-1-yl)-2-methoxyphenol 22b was identified as a potent antiproliferative compound with an IC₅₀ value of 0.39 mM in MCF-7 breast cancer cells, 0.77 mM in triple-negative MDA-MB-231 breast cancer cells, and 0.37 mM in leukemia HL-60 cells. In addition, compound 22b demonstrated potent activity in the sub-micromolar range against the NCI 60 cancer cell line panel including prostate, melanoma, colon, leukemia, and non-small cell lung cancers. G₂/M phase cell cycle arrest and the induction of apoptosis in MCF-7 cells together with inhibition of tubulin polymerization were demonstrated. Immunofluorescence studies confirmed that compound 22b targeted tubulin in MCF-7 cells, while computational docking studies predicted binding conformations for 22b in the colchicine binding site of tubulin. Compound 22b also selectively inhibited aromatase. Conclusions: Based on the results obtained, these novel compounds are suitable candidates for further investigation as antiproliferative microtubule-targeting agents for breast cancer. Full article

Background/Objectives: Cancer remains one of the major challenges of our century. Organometallic ruthenium complexes are gaining recognition as a highly promising group of compounds in the development of cancer treatments. Methods: Building on the auspicious results obtained for [Ru(η⁵-C₅H₅)(PPh₃)(bipy)][CF₃SO₃] (TM34), our focus has shifted to examining the effects of incorporating bioactive ligands into the TM34 framework, particularly within the cyclopentadienyl ring. Results: In this study, we report the synthesis and characterization of two new ruthenium(II) complexes with the general formula [Ru(η⁵-C₅H₄CCH₃=R)(PPh₃)(bipy)][CF₃SO₃], where R represents a nicotinic acid derivative (NNHCO(py-3-yl)) (1) or an isoniazid derivative (NNHCO(py-4-yl)) (2). The complexes were fully characterized using a combination of spectroscopic techniques and computational analysis, revealing the presence of E/Z-hydrazone isomerism. Stability studies confirmed the robustness of both complexes in biological media, with compound 1 maintaining good stability in buffer solutions mimicking physiological (pH 7.4) and tumor-like (pH 6.8) environments. The cytotoxicity of the complexes was evaluated in vitro in several human cancer cell lines, namely melanoma (A375), alveolar adenocarcinoma (A549), epidermoid carcinoma (A431), and breast cancer (MDA-MB 231). Conclusions: Both compounds exhibited moderate to high cytotoxic activity, with complex 1 showing a greater propensity to induce cell death, particularly in the A431 and MDA-MB 231 cell lines. Full article

Background/Objectives: The stimulator of interferon genes (STING) is currently accepted as a relevant target for anti-cancer therapies. Besides encouraging results showing STING agonist-induced tumor growth inhibition, in some types of tumors the effect is less prominent. We hypothesized that higher STING levels in cancer cells and the possibility of its activation determine a greater anti-cancer response. As the local administration of STING agonists induces a systemic reaction, we emphasized the importance of host tumor-induced hematological disruption in the efficiency of the therapeutic response. Methods: We investigated the response to STING stimulation in murine cancer cell lines—melanoma (B16-F10) and breast carcinoma (4T1)—and murine normal cell lines: fibroblast cells (NIH/3T3), endothelial cells (H5V), and macrophages (J774A.1). We assessed STING agonist-induced tumor growth inhibition and the therapy’s impact on the hematological system parameters and systemic cytokine release. Results: Our results underlined the improved therapeutic effect of STING activation in melanoma (B16-F10) over breast carcinoma (4T1) tumors. The outcomes reflected a high dysregulation of the hematological system in mice with developed 4T1 tumors, which may support persistent inflammation and impede STING-induced therapeutic effects. Moreover, among typical cytokines produced following STING activation, CCL2 fold change was the one that increased the most in the serum of B16-F10-bearing mice and differentiated the observed response to the STING agonist between investigated tumor models. Conclusions: The current study provides new evidence of the different responses to STING activation among two poorly immunogenic tumor models. The high abundance of STING in B16-F10 cells and the possibility of its activation is linked with improved therapeutic response in vivo compared to 4T1. The effect also seems to be connected with a less dysregulated hematological system in mice with B16-F10 tumors over mice with 4T1 tumors. This highlighted the need for general insight into tumor-induced local and systemic responses to the efficiency of the proposed therapy. Full article