Cobalt-ferrite magnetic nanoparticles (MNPs) exhibiting three distinct morphologies: spherical, cubic, and octopod-like, with perfect shape resolution and a very narrow size distribution, were successfully synthesised by the thermal decomposition method. The influence of particle shape on the structural, magnetic, and magneto-thermal properties was systematically investigated. The magneto-thermal performance was evaluated under AC fields with varying amplitudes and frequencies and quantified using the SAR and ILP parameters. A pronounced dependence of heating efficiency on particle morphology was observed. Cubic nanoparticles exhibited the highest magneto-thermal performance, reaching SAR values up to 411 W/g at applied field ∼20 kA/m and 728 kHz, whereas spherical nanoparticles showed negligible heating, and octopod particles exhibited intermediate performance. These differences are interpreted within the framework of linear response theory, highlighting the roles of effective magnetic anisotropy and interparticle interactions in governing the magneto-thermal response. The response of A549 and HT-29 cancer cells to cobalt-ferrite nanoparticles was found to be strongly concentration-dependent. At a concentration of 100 µg/mL, cubic nanoparticles exhibited the weakest inhibitory effect, while lower concentrations were well tolerated without a significant morphology-dependent effect. Overall, the results underline the importance of morphology control in the design of efficient and biocompatible cobalt-ferrite nanoparticles for magnetic hyperthermia applications.

Coumarins are known to provide promising scaffolds for the development of new anticancer drugs, yet their multitarget biological profiles remain insufficiently explored. This study presents a comprehensive evaluation of four newly synthesized 4-substituted 7-hydroxycoumarin derivatives C1–C4, highlighting their combined antiproliferative, enzyme-inhibitory, and pharmacokinetic properties. The compounds were tested for their cytotoxic effects on A549 lung carcinoma cells and CCD-18Co fibroblasts, inhibition of topoisomerase I (Topo I), and binding interactions with human serum albumin (HSA). Derivatives C1, C2, and C4 showed selective suppression of A549 metabolic activity and proliferation, while exhibiting minimal toxicity toward non-cancerous fibroblasts. All compounds inhibited Topo I to varying degrees, with C1 displaying the highest potency, indicating that specific hydroxyl group arrangements are crucial for enzyme inhibition. Fluorescence spectroscopy and molecular docking revealed moderate to high HSA affinity (104–106 M−1) and predominantly single-site binding, supporting their favorable plasma transport potential. Thermodynamic analysis showed distinct interaction patterns: C1 and C2 formed complexes stabilized primarily by hydrogen bonds and van der Waals forces, whereas C3 and C4 interacted mainly through hydrophobic forces. Competitive displacement assays identified Sudlow site I as the principal binding region, although molecular docking studies also suggested the possible involvement of site III. Overall, this work introduces a novel series of coumarin derivatives with a clearly defined multitarget anticancer profile which combines selective cytotoxicity, effective Topo I inhibition, and strong pharmacokinetic characteristics, thereby underscoring the potential of these derivatives as lead structures for further anticancer drug development.

This study reports the synthesis, characterization, and biological evaluation of copper(II) complexes with (3E)-3-(1-{[(pyridin-2-yl)methyl]amino}ethylidene)-3,4-dihydro-2H-benzopyran-2,4-dione (HL) and its newly designed derivatives bearing a halogen atom X in the position 6 (6-FHL, 6-ClHL, and 6-BrHL). The coumarin-based ligands were synthesized via a multistep organic synthesis route and characterized using IR, and NMR spectroscopy. A total of 9 new copper(II) complexes were prepared, divided in two distinct series: chloride-containing complexes [Cu(L/6-XL)Cl] (1-4) and nitrate-based complexes [Cu(L)(H2O)(NO3)] (5) and [Cu(6-XL)(NO3)]x (6-9). All complexes were characterised by IR spectroscopy, mass spectroscopy (1-8), and elemental analysis. Also structural characterization by single-crystal X-ray diffraction for complexes 5-9 was done. The stability of all the complexes in solution was confirmed by UV-Vis spectroscopy. All complexes and free ligands were screened for their cytotoxic activity against MDA-MB-231 (breast) and HCT 116 (colorectal) human cancer cell lines, with comparisons to healthy PDL-MSC cells. Based on IC50 values, complexes 3, 4, and 7 emerged as the most promising candidates and were selected for further investigation. Detailed in vitro antitumor studies were carried out, including cell proliferation assays, quantification of cell number and viability, and flow cytometry analyses. Moreover, comprehensive evaluations such as Hirshfeld surface analysis, DNA-binding affinity (using fluorescence competitive dye displacement assay with ethidium bromide and viscometry), human serum albumin (HSA) interaction, antioxidant activity, and lipophilicity assessments were performed to further explore their biomedical potential.

Skyrin (SKR) is a bisanthraquinone secondary metabolite found in various fungi and plant species. Although it has demonstrated anticancer potential, its mechanism of action remains largely unclear. In this study, we investigated the biological effects of SKR in multiple cancer cell lines to further understand its molecular activity. We first examined the mechanism of previously reported SKR-induced upregulation of death receptor 5 (DR5) in HCT 116 and HT-29 colorectal cancer cells. Western blot analysis and siRNA experiments revealed that this upregulation was independent of the tumor suppressor protein p53 and instead implicated endoplasmic reticulum stress-inducible transcription factor CHOP. We next investigated whether SKR can induce reactive oxygen species formation. However, flow cytometry analysis demonstrated, for the first time, that SKR exhibited antioxidant activity in live cells. Finally, we explored the potential interaction between SKR and breast cancer-resistance protein (BCRP) using the HL-60 leukemic cell line with low BCRP expression and its BCRP-overexpressing subclone (cBCRP). Inhibition of BCRP led to increased intracellular accumulation of SKR in cBCRP cells, suggesting that SKR is a novel BCRP substrate. Furthermore, BCRP inhibition sensitized these cells to SKR treatment, as reflected by decreased metabolic activity and a reduced total number of cells. In conclusion, our findings provide new mechanistic insight into the anticancer effects of SKR. These results support the potential application of SKR in cancer prevention and therapy, particularly in tumors with dysfunctional p53.

Photodynamic therapy (PDT) is an effective, minimally invasive treatment for certain cancers that uses photosensitizers (PSs) to selectively destroy tumor cells upon light activation. However, the breast cancer resistance protein (BCRP) plays a critical role in limiting PDT efficacy through active efflux of various PSs from the cancer cells. Hypericin (HY), a potent and promising natural PS, is also a preferential BCRP substrate, and its cytotoxic effect in PDT is reduced in BCRP-overexpressing cells. Thus, the main aim of our study was to investigate the potential of the modulators of signaling molecules possibly involved in BCRP regulation to sensitize cancer cells (A549, HT-29, RPMI-8226, and RPMI-8226/MR20) to hypericin-mediated PDT (HY-PDT). We assessed the effects of inhibitors of epidermal growth factor receptor (EGFR) (Tyr - tyrphostin AG 1478) and c-Jun N-terminal kinase (JNK) (SP - SP600125, Lico - licochalcone A), as well as protein kinase C (PKC) activator (TPA) and inhibitor (Rot - rottlerin). Our results showed that all modulators enhanced HY-PDT efficacy, but the extent of sensitization, as well as the specific effects, varied depending on the cell line. Pretreatment with Tyr, SP, and Lico significantly improved HY-PDT in RPMI-8226 and RPMI-8226/MR20 cells, while Rot pretreatment had the strongest effect in A549 and HT-29 cells. More importantly, the sensitizing effects of the inhibitors were linked to increased intracellular HY accumulation, indicating reduced BCRP efflux activity. While the exact mechanisms behind these effects require further investigation, our findings suggest that targeting BCRP and associated signaling pathways could enhance PDT outcomes in cancer treatment.

Water-based magnetic fluids were prepared using La0.80Ag0.15MnO3-delta magnetic carriers with the maximal Curie temperature TC = 319.5 K (46.4 degrees C). The starting nanoparticles mainly consisted from agglomerates with average particle size between 43 and 47 nm. Separation of nanoparticles from aggregates using a stirred ball mill in combination with the use of anionic sodium dodecyl sulphate surfactant led to the preparation of electrostatically stabilised magnetic fluid with average hydrodynamic size of particles xav less than 75 nm. A combination of mechanical grinding, sonication and etching in different acids was used to prepare Dextran 40 kDa sterically and carboxymethyl-dextran 15 kDa electrosterically stabilised magnetic fluid with average hydrodynamic size of particles ranging between 50 and 190 nm. Milling and etching results in reduction of TC of about 3 K, etching causes a drastic decrease in saturation magnetization, but the magnetocaloric properties are unaffected by the preparation of the magnetic fluid, only the magnetic entropy change is reduced by three orders of magnitude. Magnetic carrier has the potential to reach the desired magnetic heating temperature T = 43.6 degrees C for applications in hyperthermia and magnetic fluids are capable to reach T = 38.1 degrees C by magnetic heating. The maximal specific absorption rate of magnetic carrier SAR = 134.7 W/g and in the case of magnetic fluid SAR = 41.9 W/g. The synthesized nanoparticles and the prepared magnetic fluids may represent materials with potential in cancer treatment, as the most pronounced effect was observed in the case of lung cancer cell line A549. Analysed nanoparticles induced a decrease in metabolic activity even at relatively low concentrations.

In this study, a novel silver(I) complex [Ag(HL1)2]NO3 (AgHL1) with coumarin derivative (3E)-3-(1-{[(pyridin-2-yl)methyl]amino}ethylidene)-3,4-dihydro-2H-benzopyran-2,4-dione (HL1) was prepared. The compounds HL1 and AgHL1 were characterized by IR and NMR spectroscopy, elemental analysis, and single crystal X-ray structural analysis. Specifically, the single crystal X-ray analysis determined the structures of both compounds HL1 and AgHL1 in their solid state, while NMR spectroscopy was used for structural determination in a solution. The HL1 proved to be a monodentate ligand and is coordinated to the Ag(I) atom through a nitrogen atom from the 2-picolylamine fragment. In the complex AgHL1, two molecules of neutral HL1 are coordinated forming a nearly linear N-Ag-N arrangement. An uncoordinated nitrate anion balances the positive charge of the complex cation. NMR spectroscopy also confirmed the stability of AgHL1 in DMSO-d6 for 3 days. In vitro cytotoxicity of HL1 and AgHL1 was performed over two cancerous cell lines A549 and HT-29 and their selectivity was verified on a healthy CCD-18Co cell line. AgHL1 exhibited low anticancer nonselective activity while the ligand was inactive. Also, the complex shows better antimicrobial activity than the positive controls on the Pseudomonas aeruginosa standard and clinical strain as well as on the tested molds.

Atranorin (ATR) is one of lichens’ many known secondary metabolites. Most current studies have investigated the various effects of ATR in vitro and only sporadically in vivo. The latest data indicate that ATR may have anxiolytic/antidepressive effects. This study aimed to analyze the potential of ATR in a depression-like state in male Wistar rats. Pregnant females were stressed by restricting their mobility in the final week of pregnancy three times a day for 45 min each, for three following days. After birth, progeny aged 60 days was stressed repeatedly. The male progeny was divided into three groups as follows: CTR group as a healthy control (n = 10), DEP group as a progeny of restricted mothers (n = 10), and ATR group as a progeny of restricted mothers, treated daily for one month with ATR (n = 10; 10 mg/kg of body weight, p.o.). Our results show that ATR acts as an antioxidant and markedly changes animal behavior. Concomitantly, hippocampal neurogenesis increases in the hilus and subgranular zone, together with the number of NeuN mature neurons in the hilus and CA1 regions. Our results indicate a potential antidepressant/anxiolytic effect of ATR. However, further studies in this area are needed.

We report the synthesis of fine (& SIM; 5 nm) citric acid capped CoFe2O4 (CA-CoFe2O4) nanoparticles by co -precipitation method at different pH conditions that changes gradually from 6 to 11. Structural and mag-netic characterization performed by TEM, XRD and SQUID confirm that synthesis under lower pH (6 and 9) leads to the formation of citric acid shell covering the individual nanoparticles. Capping layer increases inter-particle distance what results in the decrease of the interaction strength. On the other hand, higher pH (10 and 11) apparently hampers the proper formation of the layer that, in consequence, builds thinner organic coating. Therefore, individual nanoparticles are in closer contact and acting of strong mutual in-teractions results in the formation of larger agglomerates with pomegranate-like structure. For biomedical applications of studied systems the viability study on A549 lung cancer cells was performed. The high power confocal analyses confirmed the presence of nanoparticles both in the nucleus as well as in the perikaryon of the cells and no changes in morphology indicating the adverse effect of nanoparticles were observed.& COPY; 2023 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

In this contribution, a novel coumarin-derivative ligand, and its silver(I) complex are reported. Ligand 3-(1-(2-pyridylamino)ethylidene)-2H-chromene-2,4-dione (HL) was prepared by reaction of 3-acetyl-4-hydroxycoumarin with 2-picolyl amine. Further, complex [Ag(HL)2]NO3 was prepared and both compounds were characterized by physico-chemical methods such as IR and NMR spectroscopy, elemental analysis, and structure of the ligand and the complex was confirmed by X-ray analysis. The stability of both compounds was measured by NMR spectroscopy. MTT assay and cell proliferation assay on human lung adenocarcinoma cell line A549 and human colorectal adenocarcinoma cell line HT-29 showed that complex was more active than free HL ligand.

The presence of key hypoxia regulators, namely, hypoxia-inducible factor (HIF)-1α or HIF-2α, in tumors is associated with poor patient prognosis. Hypoxia massively activates several genes, including the one encoding the BCRP transporter that proffers multidrug resistance to cancer cells through the xenobiotic efflux and is a determinant of the side population (SP) associated with cancer stem-like phenotypes. As natural medicine comes to the fore, it is instinctive to look for natural agents possessing powerful features against cancer resistance. Hypericin, a pleiotropic agent found in Hypericum plants, is a good example as it is a BCRP substrate and potential inhibitor, and an SP and HIF modulator. Here, we showed that hypericin efficiently accumulated in hypoxic cancer cells, degraded HIF-1/2α, and decreased BCRP efflux together with hypoxia, thus diminishing the SP population. On the contrary, this seemingly favorable result was accompanied by the stimulated migration of this minor population that preserved the SP phenotype. Because hypoxia unexpectedly decreased the BCRP level and SP fraction, we compared the SP and non-SP proteomes and their changes under hypoxia in the A549 cell line. We identified differences among protein groups connected to the epithelial-mesenchymal transition, although major changes were related to hypoxia, as the upregulation of many proteins, including serpin E1, PLOD2 and LOXL2, that ultimately contribute to the initiation of the metastatic cascade was detected. Altogether, this study helps in clarifying the innate and hypoxia-triggered resistance of cancer cells and highlights the ambivalent role of natural agents in the biology of these cells.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Abstract Cell death is an essential process occurring during the development of the central nervous system. Despite the availability of wide range of commercially produced antibodies against various apoptotic markers, data regarding the apoptosis in intact spinal cord during postnatal development and adulthood are mostly missing. This study aimed to investigate the apoptosis in the rat spinal cord at different stages of ontogenesis (8, 29 and 90 postnatal days). For this purpose, we used immunofluorescent detection of two widely used apoptotic markers, activated caspase-3 (aC3) and cleaved PARP (cPARP). Surprisingly, we found significant discrepancy between the amounts of aC3+ cells and PARP+ cells, varying with ratio around 500:1–5,000:1 in the rat spinal cord in all postnatal time points. Majority of aC3+ cells were glial cells and did not exhibit apoptotic phenotype. In contrast with the results of in vivo study, in vitro analysis of primary cell culture derived from neonatal rat spinal cord, treated with apoptotic inductor staurosporine, revealed similar onset of occurrence of both markers in cells subjected to apoptosis. Gene expression analysis of spinal cord tissue revealed elevated expression of Birc4 (XIAP), Birc2 and Birc5 (Survivin) genes, which are known as potent inhibitors of apoptosis. Our data indicates that the activated caspase-3 is not an exclusive marker of apoptosis, especially in glial cells, due its possible presence in inhibited forms and/or its participation in other, non-apoptotic roles. Therefore, in the light of our recent results, cPARP appears to be more appropriate marker for detection of apoptosis.

Half-sandwich complexes [Ru(η6-pcym)(L1)X]PF6 (1, 3) and [Ir(η5-Cp*)(L1)X]PF6 (2, 4) featuring a thiadiazole-based ligand L1 (2-(furan-2-yl)-5-(pyridin-2-yl)-1,3,4-thiadiazole) were synthesized and characterized by varied analytical methods, including single-crystal X-ray diffraction (X = Cl or I, pcym = p-cymene, Cp* = pentamethylcyclopentadienyl). The structures of the molecules were analysed and interpreted using computational methods such as Density Functional Theory (DFT) and Quantum Theory of Atoms in Molecules (QT-AIM). A 1H NMR spectroscopy study showed that complexes 1-3 exhibited hydrolytic stability while 4 underwent partial iodido/chlorido ligand exchange in phosphate-buffered saline. Moreover, 1-4 demonstrated the ability to oxidize NADH (reduced nicotinamide adenine dinucleotide) to NAD+ with Ir(III) complexes 2 and 4 displaying higher catalytic activity compared to their Ru(II) analogues. None of the complexes interacted with reduced glutathione (GSH). Additionally, 1-4 exhibited greater lipophilicity than cisplatin. In vitro biological analyses were performed in healthy cell lines (CCD-18Co colon and CCD-1072Sk foreskin fibroblasts) as well as in cisplatin-sensitive (A2780) and -resistant (A2780cis) ovarian cancer cell lines. The results indicated that Ir(III) complexes 2 and 4 had no effect on human fibroblasts, demonstrating their selectivity. In contrast, complexes 1 and 4 exhibited moderate inhibitory effects on the metabolic and proliferation activities of the cancer cells tested (selectivity index SI > 3.4 for 4 and 2.6 for cisplatin; SI = IC50(A2780)/IC50(CCD-18Co)), including the cisplatin-resistant cancer cell line. Based on these findings, it is possible to emphasize that mainly complex 4 could represent a further step in the development of selective and highly effective anticancer agents, particularly against resistant tumour types.

It is more than sixty years since the era of modern photodynamic therapy (PDT) for cancer began. Enhanced selectivity for malignant cells with a reduced selectivity for non-malignant cells and good biocompatibility along with the limited occurrence of side effects are considered to be the most significant advantages of PDT in comparison with conventional therapeutic approaches, e.g., chemotherapy. The phenomenon of multidrug resistance, which is associated with drug efflux transporters, was originally identified in relation to the application of chemotherapy. Unfortunately, over the last thirty years, numerous papers have shown that many photosensitizers are the substrates of efflux transporters, significantly restricting the effectiveness of PDT. The concept of a dynamic nanoplatform offers a possible solution to minimize the multidrug resistance effect in cells affected by PDT. Indeed, recent findings have shown that the utilization of nanoparticles could significantly enhance the therapeutic efficacy of PDT. Additionally, multifunctional nanoplatforms could induce the synergistic effect of combined treatment regimens, such as PDT with chemotherapy. Moreover, the surface modifications that are associated with nanoparticle functionalization significantly improve the target potential of PDT or chemo-PDT in multidrug resistant and cancer stem cells.

A series of novel acridine N-acylhydrazone derivatives have been synthesized as potential topoisomerase I/II inhibitors, and their binding (calf thymus DNA—ctDNA and human serum albumin—HSA) and biological activities as potential anticancer agents on proliferation of A549 and CCD-18Co have been evaluated. The acridine-DNA complex 3b (-F) displayed the highest Kb value (Kb = 3.18 × 103 M−1). The HSA-derivatives interactions were studied by fluorescence quenching spectra. This method was used for the calculation of characteristic binding parameters. In the presence of warfarin, the binding constant values were found to decrease (KSV = 2.26 M−1, Kb = 2.54 M−1), suggesting that derivative 3a could bind to HSA at Sudlow site I. The effect of tested derivatives on metabolic activity of A549 cells evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide or MTT assay decreased as follows 3b(-F) > 3a(-H) > 3c(-Cl) > 3d(-Br). The derivatives 3c and 3d in vitro act as potential dual inhibitors of hTopo I and II with a partial effect on the metabolic activity of cancer cells A594. The acridine-benzohydrazides 3a and 3c reduced the clonogenic ability of A549 cells by 72% or 74%, respectively. The general results of the study suggest that the novel compounds show potential for future development as anticancer agents.

Skyrin (SKR) is a plant bisanthraquinone secondary metabolite from the Hypericum genus with potential use in anticancer therapy. However, its effect and mechanism of action are still unknown. The negative effect of SKR on HCT 116 and HT-29 cancer cell lines in hypoxic and normoxic conditions was observed. HCT 116 cells were more responsive to SKR treatment as demonstrated by decreased metabolic activity, cellularity and accumulation of cells in the G1 phase. Moreover, an increasing number of apoptotic cells was observed after treatment with SKR. Based on the LC-MS comparative proteomic data from hypoxia and normoxia (data are available via ProteomeXchange with the identifier PXD019995), SKR significantly upregulated Death receptor 5 (DR5), which was confirmed by real-time qualitative PCR (RT-qPCR). Furthermore, multiple changes in the Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-activated cascade were observed. Moreover, the reversion of TRAIL resistance was observed in HCT 116, HT-29 and SW620 cell lines, even in hypoxia, which was linked to the upregulation of DR5. In conclusion, our results propose the use of SKR as a prospective anticancer drug, particularly as an adjuvant to TRAIL-targeting treatment to reverse TRAIL resistance in hypoxia.

A549 human lung carcinoma cell lines were treated with a series of new drugs with both tacrine and coumarin pharmacophores (derivatives 1a–2c) in order to test the compounds’ ability to inhibit both cancer cell growth and topoisomerase I and II activity. The ability of human topoisomerase I (hTOPI) and II to relax supercoiled plasmid DNA in the presence of various concentrations of the tacrine-coumarin hybrid molecules was studied with agarose gel electrophoresis. The biological activities of the derivatives were studied using MTT assays, clonogenic assays, cell cycle analysis and quantification of cell number and viability. The content and localization of the derivatives in the cells were analysed using flow cytometry and confocal microscopy. All of the studied compounds were found to have inhibited topoisomerase I activity completely. The effect of the tacrine-coumarin hybrid compounds on cancer cells is likely to be dependent on the length of the chain between the tacrine and coumarin moieties (1c, 1d = tacrine-(CH2)8–9-coumarin). The most active of the tested compounds, derivatives 1c and 1d, both display longer chains.

A series of novel C4-C7-tethered biscoumarin derivatives (12a–e) linked through piperazine moiety was designed, synthesized, and evaluated biological/therapeutic potential. Biscoumarin 12d was found to be the most effective inhibitor of both acetylcholinesterase (AChE, IC50 = 6.30 µM) and butyrylcholinesterase (BChE, IC50 = 49 µM). Detailed molecular modelling studies compared the accommodation of ensaculin (well-established coumarin derivative tested in phase I of clinical trials) and 12d in the human recombinant AChE (hAChE) active site. The ability of novel compounds to cross the blood–brain barrier (BBB) was predicted with a positive outcome for compound 12e. The antiproliferative effects of newly synthesized biscoumarin derivatives were tested in vitro on human lung carcinoma cell line (A549) and normal colon fibroblast cell line (CCD-18Co). The effect of derivatives on cell proliferation was evaluated by MTT assay, quantification of cell numbers and viability, colony-forming assay, analysis of cell cycle distribution and mitotic activity. Intracellular localization of used derivatives in A549 cells was confirmed by confocal microscopy. Derivatives 12d and 12e showed significant antiproliferative activity in A549 cancer cells without a significant effect on normal CCD-18Co cells. The inhibition of hAChE/human recombinant BChE (hBChE), the antiproliferative activity on cancer cells, and the ability to cross the BBB suggest the high potential of biscoumarin derivatives. Beside the treatment of cancer, 12e might be applicable against disorders such as schizophrenia, and 12d could serve future development as therapeutic agents in the prevention and/or treatment of Alzheimer’s disease.

Formation of new neurons and glial cells in the brain is taking place in mammals not only during prenatal embryogenesis but also during adult life. As an enhancer of oxidative stress, ionizing radiation represents a potent inhibitor of neurogenesis and gliogenesis in the brain. It is known that the pineal hormone melatonin is a potent free radical scavenger and counteracts inflammation and apoptosis in brain injuries. The aim of our study was to establish the effects of melatonin on cells in the hippocampus and selected forms of behaviour in prenatally irradiated rats. The male progeny of irradiated (1 Gy of gamma rays; n = 38) and sham-irradiated mothers (n = 19), aged 3 weeks or 2 months, were used in the experiment. Melatonin was administered daily in drinking water (4 mg/kg b. w.) to a subset of animals from each age group. Prenatal irradiation markedly suppressed proliferative activity in the dentate gyrus in both age groups. Melatonin significantly increased the number of proliferative BrdU-positive cells in hilus of young irradiated animals, and the number of mature NeuN-positive neurons in hilus and granular cell layer of the dentate gyrus in these rats and in CA1 region of adult irradiated rats. Moreover, melatonin significantly improved the spatial memory impaired by irradiation, assessed in Morris water maze. A significant correlation between the number of proliferative cells and cognitive performances was found, too. Our study indicates that melatonin may decrease the loss of hippocampal neurons in the CA1 region and improve cognitive abilities after irradiation.