Cytotoxicity induced by three commercial neonicotinoid insecticide formulations in differentiated human neuroblastoma SH-SY5Y cells.

Background: Neonicotinoid insecticides are used worldwide for crop protection. They act as agonists at postsynaptic nicotinic acetylcholine receptors (nAChRs), disrupting normal neurotransmission in target insects. Human exposure is high due to the widespread use of neonicotinoids and their residues in food. This study aimed to evaluate the in vitro neurotoxicity of three neonicotinoid commercial formulations Much 600 FS® (imidacloprid 600 g L-1), Evidence 700 WG® (imidacloprid 700 g kg-1), and Actara 250 WG® (thiamethoxam 250 g kg-1) in differentiated human neuroblastoma SH-SY5Y cell line. Methods: Cells were incubated with the pesticides for 96 h, and the cytotoxicity was evaluated through the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium·bromide (MTT) reduction and neutral red (NR) uptake assays. Toxicological pathways such as reactive oxygen (ROS) and nitrogen species (RNS) production, mitochondrial membrane potential, cell death mode, and the expression of the pro-apoptotic protein Bax were also evaluated. Results: EC50 values of 266.4, 4,175, and 653.2 mg L-1 were found for Much®, Evidence® and Actara®, respectively. Significant increases in ROS and RNS generation were observed for all pesticides, while mitochondrial membrane potential and Bax protein expression showed no significant changes. Analysis of cell death mode revealed an increase in early apoptotic cells. Conclusion: Therefore, neonicotinoid insecticides are potentially neurotoxic, reinforcing concerns about human exposure to these commercial formulations.

In silico and in vitro study of FLT3 inhibitors and their application in acute myeloid leukemia.

Acute myeloid leukemia (AML) is the most common hematological cancer in the adult population worldwide. Approximately 35% of patients with AML present internal tandem duplication (ITD) mutations in the FMS­like tyrosine kinase 3 (FLT3) receptor associated with poor prognosis, and thus, this receptor is a relevant target for potential therapeutics. Tyrosine kinase inhibitors (TKIs) are used to treat AML; however, their molecular interactions and effects on leukemic cells are poorly understood. The present study aimed to gain insights into the molecular interactions and affinity forces of four TKI drugs (sorafenib, midostaurin, gilteritinib and quizartinib) with the wild­type (WT)­FLT3 and ITD­mutated (ITD­FLT3) structural models of FLT3, in its inactive aspartic acid­phenylalanine­glycine motif (DFG­out) and active aspartic acid­phenylalanine­glycine motif (DFG­in) conformations. Furthermore, the present study evaluated the effects of the second­generation TKIs gilteritinib and quizartinib on cancer cell viability, apoptosis and proliferation in the MV4­11 (ITD­FLT3) and HL60 (WT­FLT3) AML cell lines. Peripheral blood mononuclear cells (PBMCs) from a healthy volunteer were included as an FLT3­negative group. Molecular docking analysis indicated higher affinities of second­generation TKIs for WT­FLT3/DFG­out and WT­FLT3/DFG­in compared with those of the first­generation TKIs. However, the ITD mutation changed the affinity of all TKIs. The in vitro data supported the in silico predictions: MV4­11 cells presented high selective sensibility to gilteritinib and quizartinib compared with the HL60 cells, whereas the drugs had no effect on PBMCs. Thus, the current study presented novel information about molecular interactions between the FLT3 receptors (WT or ITD­mutated) and some of their inhibitors. It also paves the way for the search for novel inhibitory molecules with potential use against AML.

Phytotoxic and Cytogenetic Assessment of Glycerol Triazole Derivatives in Model Plants and Weeds.

Weed invasion represents a challenge for farmers, who typically manage it with herbicides. However, this approach raises concerns about environmental and human health, as well as increasing resistance in these plants with continued use. Therefore, exploring alternative methods, such as heterocyclic compounds, triazoles, is essential due to their biological and environmental relevance. This study aimed to evaluate the effects of twelve 1,2,3-triazoles on the germination and early development of Lactuca sativa, Bidens pilosa, and Lolium multiflorum, as well as their impact on cell division in the cells of L. sativa. Triazole derivatives 4a, 4b, 4c, 4g, 4h, 4i, 4k, and 4l exhibited phytotoxicity, showing varying levels of inhibition in germination, germination speed index, and root growth. Chlorinated compounds were the most detrimental to lettuce development. B. pilosa was notably affected by compounds 4h, 4i, 4k, and 4l, while L. multiflorum responded most to triazoles 4c and 4l, with effectiveness comparable to that of the herbicide glyphosate. All derivatives, except 4l, exhibited aneugenic mechanisms of action, and 4a, 4b, 4c, 4e, 4f, and 4g showed clastogenic effects. This study demonstrated the potential of triazoles as effective agents against weed growth, with mechanisms that warrant further investigation for agricultural applications.

Effects of Arborvitae (Thuja plicata) Essential Oil on Cervical Cancer Cells: Insights into Molecular Mechanisms.

AIMS: This study aimed to assess the effects of AEO in an in vitro model of cell lines derived from cervical cancer-namely, HeLa and SiHa-by screening for AEO's cytotoxic properties and examining its influence on the modulation of gene expression. BACKGROUND: Cervical cancer stands as a prevalent global health concern, affecting millions of women worldwide. The current treatment modalities encompass surgery, radiation, and chemotherapy, but significant limitations and adverse effects constrain their effectiveness. Therefore, exploring novel treatments that offer enhanced efficacy and reduced side effects is imperative. Arborvitae essential oil, extracted from Thuja Plicata, has garnered attention for its antimicrobial, anti-inflammatory, immunomodulatory, and tissue-remodeling properties; however, its potential in treating cervical cancer remains uncharted. OBJECTIVE: The objective of this study was to delve into the molecular mechanisms induced by arborvitae essential oil in order to learn about its anticancer effects on cervical cancer cell lines. METHODS: The methods used in this study were assessments of cell viability using WST-1 and annexin V- propidium iodide, mRNA sequencing, and subsequent bioinformatics analysis. RESULTS: The findings unveiled a dose-dependent cytotoxic effect of arborvitae essential oil on both HeLa and SiHa cell lines. Minor effects were observed only at very low doses in the HaCaT non-tumorigenic human keratinocyte cells. RNA-Seq bioinformatics analysis revealed the regulatory impact of arborvitae essential oil on genes enriched in the following pathways: proteasome, adherens junctions, nucleocytoplasmic transport, cell cycle, proteoglycans in cancer, protein processing in the endoplasmic reticulum, ribosome, spliceosome, mitophagy, cellular senescence, and viral carcinogenesis, among others, in both cell lines. It is worth noting that the ribosome and spliceosome KEGG pathways are the most significantly enriched pathways in HeLa and SiHa cells. CONCLUSION: Arborvitae essential oil shows potential as a cytotoxic and antiproliferative agent against cervical cancer cells, exerting its cytotoxic properties by regulating many KEGG pathways.

Cytotoxicity, chemical, and nutritional profile evaluation of biomass extracts of the Lemna aequinoctialis (duckweed) aquatic plant.

Lemna aequinoctialis (duckweed) is the smallest and fast-growing aquatic plant species producing protein-rich biomass with high protein nutritional value, phytoremediation capacity, and nutrient removal from wastewater. Duckweed may also be used as a new potential bioreactor for biological products, such as vaccines, antibodies, and pharmaceutical proteins. Based upon the potential importanc of L. aequinoctialis in phytoremediation and as a bioreactor the aim of this study was to (1) characterize the chemical and nutritional profiles of L. aequinoctialis biomass utilizing an integrated multi-trophic aquaculture system (IMTA) and a pond, and (2) investigate the cytotoxic potential of different concentrations of organic extracts and fractions using the MTT bioassay. EDXRF and ICP-MS analyses indicated the presence of trace elements in lower amounts in relation to the biomass of L. aequinoctialis in the lagoon, emphasizing the importance of plant inclusion management to reduce bioaccumulation of these elements. Analysis of mineral profiles, fatty acids, and amino acids indicated a satisfactory nutritional composition for the use of biomass as a bioproduct. Pigment analysis showed a high concentration of carotenoids, especially astaxanthin. After standardizing the controls, the MTT cell viability test was carried out utilizing rat hepatoma cell line (HTC), which are metabolizing cells that were treated with aqueous or ethanolic extracts and the dichloromethane, ethyl acetate, and methanol fractions at different concentrations. No apparent cytotoxic potential was observed following treatments, since there was no significant reduction in cell viability. Therefore, this study provides information regarding the biomass of L. aequinoctialis derived from the IMTA system, which might support further research into the application of this species as a bioproduct.

Evaluation of the cytotoxicity of new formulations of cariostatic agents containing nano silver fluoride: an in vitro study.

The objective of the study was to assess the indirect cytotoxicity of 600 ppm and 1500 ppm nano silver fluoride (NSF) compared to other commercial cariostatic agents. 56 dentin discs with 0.4 mm in thickness were obtained from intact human molars and adapted to artificial pulp chambers (APCs). The discs were divided into seven groups according to treatment (n = 8): no treatment (positive control-PC), 29% hydrogen peroxide (negative control-NC), 30% Cariestop (CS30), 38% Riva Star (RS38), 38% Advantage Arrest (AA38), 600 ppm NSF (NSF600), and 1500 ppm NSF (NSF1500). The cariostatic agents were applied on the occlusal surface of the dentin discs (facing upward), and the pulp surface (facing downward) remained in contact with the culture medium. Immediately after the treatments, the extracts (DMEM + cariostatic agent components diffused through the discs) were collected and applied to MDPC-23 cells, which were assessed for viability (CV-alamarBlue, live/dead), adhesion/spreading (F-actin), alkaline phosphatase (ALP) activity, and mineralization nodule (MN) formation. The data were statistically analyzed by ANOVA/Games-Howell (p = 0.05). CV and ALP activity in CS30, RS38, AA38, and NSF600 were similar to PC (p > 0.05). MN formation significantly decreased only in NC, CS30, RS38, and AA38 compared to PC (p < 0.001). Only NSF600 and NSF1500 did not differ from PC (p > 0.05) with mineralization nodules, and this specific cell activity significantly decreased in all other groups (p < 0.05). NSF solutions (600 ppm and 1500 ppm) did not cause transdentinal toxicity on MDPC-23 cells.

Exploring the toxicity profile of coriander (C. sativum L.) essential oil: implications for translational toxicological research.

The plant species C. sativum L. is a staple in cuisine and holds significant ethnopharmacological value. Its essential oil (EO) is of particular interest, yet its toxicity profile remains a subject of inquiry. This study aimed to elucidate the chemical constituents of C. sativum L. EO and evaluate its toxicity through various parameters, including cytotoxicity assays on HaCaT keratinocytes, in vivo toxicity tests on Galleria mellonella larvae, in vivo genotoxicity assessments on mice and cytotoxicity assays on human erythrocytes. Notably, major constituents such as 2-decen-1-ol, dec-(2E)-enal, and 1,6-octadien-3-ol were found to remain predominant. The IC50 value for the essential oil on the keratinocyte cell line was determined to be 60.13 ± 2.02 µg/mL. However, in vivo toxicity tests with G. mellonella larvae demonstrated safety at doses below 4.5 g/kg. Additionally, genotoxicity assessment revealed that a single dose of 20 mg/mL (5 mg/kg) did not induce a significant increase in micronuclei formation. EO concentrations above 250 µg/mL led to significant changes in human erythrocytes cell viability (p < 0.0001), resulting in over 60% hemolysis. These findings collectively suggest that the essential oil of C. sativum L. exhibits a suitable toxicity profile for conducting preclinical studies in vertebrate animal models.

In vitro and in silico evaluation of the anti-leishmania activity of synthetic chalcones.

Leishmaniasis is a group of neglected, vector-borne infectious diseases that affect millions of people around the world. The medications available for its treatment, especially in cases of visceral leishmaniasis, are old, outdated and have serious side effects. In this work, 10 chalcones were synthesised and evaluated in vitro against promastigotes and axenic amastigotes of Leishmania infantum. Compounds CP04 and CP06 were the most promising, respectively presenting IC50 values = 13.64 ± 0.25 and 11.19 ± 0.22 µM against promastigotes, and IC50 = 18.92 ± 0.05 and 22.42 ± 0.05 µM against axenic amastigotes. Only compound CP04 did not show cytotoxicity against peripheral blood mononuclear cells (PBMCs). Molecular docking studies conducted with sterol 14-alpha demethylase (CYP-51) (PDB: 3L4D) and trypanothione reductase (PDB: 5EBK) enzymes from L. infantum evidenced the great affinity of compound CP04 for these targets, presenting Moldock score values of -94.0758 and -50.5692 KJ/mol-1.

Pharmacological potential of Euphorbia tirucalliL. latex in gastric adenocarcinoma: from an ethnopharmacological perspective into new products.

Products derived from the latex of Euphorbia tirucalli were obtained through hydrolysis and column chromatography, resulting in products rich in triterpenes, ingenol 3-esters (I3E), and other derivatives from hydrolysed latex. These products underwent evaluation for their cytotoxic activity against gastric adenocarcinoma cells (AGS). Triterpene derivatives were synthesised, and the selectivity of each product was assessed. The results were compared with the previously described crude latex. Triterpenes and I3E were analysed in silico for their affinity with the active site of PKCδC1b. The hydrolysed latex (free of I3E) exhibited high cytotoxicity, albeit with reduced selectivity. Triterpenes and acetylated triterpenes were more cytotoxic than I3E, although the latter showed greater selectivity. Euphol benzoates and cinnamates showed no cytotoxicity. I3E demonstrated high affinity for the PKCδC1b. In summary, triterpenes exhibited higher cytotoxicity against AGS cells, while I3E displayed greater selectivity. Hydrolysed latex shows promise as a potential candidate for future gastric cancer treatment.

Cytotoxic and antibacterial compounds from Schinus terebinthifolia Raddi fruits.

Chromatographic procedures of extracts of Schinus terebinthifolia Raddi fruits afforded (Z)-masticadienoic (1) and 3ß-masticadienolic (2) acids, tetrahydroamentoflavone (3), and 4-O-methyl gallic acid (4). Addicionally, the derivative 6-oxo masticadienoic acid (1a) was prepared by an allylic oxidation. The chemical structures of obtained compounds were elucidated by spectrometric data analyses. Furthermore, both the semi-synthetic derivative and the metabolites were subjected to in vitro cytotoxicity against the A549 human lung cancer cell line, as well as antimicrobial activity tests. Compounds 2 and 1a exhibited cytotoxicity towards A549 cells with IC50 values of 20.13 and 6.11 µM, respectively. In the tests against pathogens, the CHCl3 and EtOAc soluble fractions of MeOH extract along with the pure compounds, exhibited antibacterial activity against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. Except for 4-O-methyl gallic acid, the other pure compounds showed inhibitory microbial activities with MIC values ranging from 0.25 µg/mL to 25 µg/mL doses.

A Novel Compound from the Phenylsulfonylpiperazine Class: Evaluation of In Vitro Activity on Luminal Breast Cancer Cells.

Breast cancer (BC) is the most common cancer in women, and is characterized by its histological and molecular heterogeneity. Luminal BC is an estrogen receptor-positive subtype, with varied clinical courses. Although BC patients are eligible for hormone therapy, both early and late relapses still occur, and thus there is a demand for new cytotoxic and selective treatment strategies for these patients. In the present study, inspired by the structure of phenylsulfonylpiperazine, a series of 20 derivatives were tested in bioassays against MCF7, MDA-MB-231 and MDA-MB-453 BC cells to discover new hit compounds. After 48 h of treatment, 12 derivatives impaired cell viability and presented significant IC50 values against at least one of the tumor lineages. Overall, the luminal BC cell line MCF7 was more sensitive to treatments. Compound 3, (4-(1H-tetrazol-1-yl)phenyl)(4-((4-chlorophenyl)sulfonyl)piperazin-1-yl)methanone, was the most promising, with IC50 = 4.48 µM and selective index (SI) = 35.6 in MCF7 cells. Compound 3 also presented significant antimigratory and antiproliferative activities against luminal BC cells, possibly by affecting the expression of genes involved in the epithelial-mesenchymal transition mechanism, upregulating E-Cadherin transcripts (CDH1). Our findings suggest that phenylsulfonylpiperazine derivatives are potential candidates for the development of new therapies, especially those targeting luminal BC.

Toward the Production of Hydroxyapatite/Poly(Ether-Ether-Ketone) (PEEK) Biocomposites: Exploring the Physicochemical, Mechanical, Cytotoxic and Antimicrobial Properties.

The development of hydroxyapatite (HAp) and polyether ether ketone (PEEK) biocomposites has been extensively studied for bone repair applications due to the synergistic properties of the involved materials. In this study, we aimed to develop HAp/PEEK biocomposites using high-energy ball milling, with HAp concentrations (20%, 40%, and 60% w/v) in PEEK, to evaluate their physicochemical, mechanical, cytotoxicity, and antimicrobial properties for potential applications in Tissue Engineering (TE). The biocomposites were characterized by structure, morphology, apparent porosity, diametral compression strength, cytotoxicity, and antimicrobial activity. The study results demonstrated that the HAp/PEEK biocomposites were successfully synthesized. The C2 biocomposite, containing 40% HAp, stood out due to the optimal distribution of HAp particles in the PEEK matrix, resulting in higher compression strength (246 MPa) and a homogeneous microstructure. It exhibited antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, with no cytotoxicity observed. These properties make the C2 biocomposite promising for regenerative medicine applications, combining mechanical strength, bioactivity, and biocompatibility.

The n-Butanol Extract Obtained from the Inner Bark of Tabebuia rosea (Bertol.) DC, Specioside, and Catalposide Induce Leukemia Cell Apoptosis in the Presence of Apicidin.

The cell signaling pathways involved in the antiproliferative activities of T. rosea inner bark remain unexplored. This study evaluated the apoptotic effects of two iridoids from the inner bark of T. rosea and apicidin on THP-1 cells. The cytotoxic effects of the extract and the pure compounds on THP-1 and Jurkat cells were also evaluated using the MTT assay. The apoptotic effect was determined by measuring the mitochondrial membrane potential. The expression of mRNA and MAPK kinase, Bax, and Bcl-2 proteins was detected by Western blotting and RT-qPCR, respectively. The extract and the compounds evaluated increased the percentage of apoptotic cells. Depolarization of the mitochondrial membrane was observed, and the number of cells in the G0/G1 phase increased. Catalposide and specioside significantly increased p38 protein expression, mostly in cells pretreated with apicidin. The p38 MAPK signaling pathway is at least one of the pathways by which the n-butanol extract obtained from Tabebuia rosea, catalposide, and specioside exerts its apoptotic effect on THP-1 cells, and this effect generates a response in the G0/G1 phase and subsequent cell death. In addition, there was depolarization of the mitochondrial membrane, an effect that was related to the participation of the proapoptotic protein Bax.

Proposing an Affordable Plasma Device for Polymer Surface Modification and Microbial Inactivation.

This study proposes an affordable plasma device that utilizes a parallel-plate dielectric barrier discharge geometry with a metallic mesh electrode, featuring a straightforward 3D-printed design. Powered by a high-voltage supply adapted from a cosmetic plasma device, it operates on atmospheric air, eliminating the need for gas flux. Surface modification of polyethylene treated with this device was characterized and showed that the elemental composition after 15 min of plasma treatment decreased the amount of C to ~80 at% due to the insertion of O (~15 at%). Tested against Candida albicans and Staphylococcus aureus, the device achieved a reduction of over 99% in microbial load with exposure times ranging from 1 to 10 min. Simultaneously, the Vero cell viability remained consistently high, namely between 91% and 96% across exposure times. These results highlight this device's potential for the surface modification of materials and various infection-related applications, boasting affordability and facilitating effective antimicrobial interventions.

Liposome preparation of alpha-arbutin: stability and toxicity assessment using mouse B16F10 melanoma cells.

Melanoma is the most aggressive type of skin cancer, with few therapeutic alternatives following metastasis development. In recent years, drug delivery-associated nanotechnology has shown promising targeted results with diminished adverse effects compared to conventional treatments. This study aimed to (1) examine the effects of plant-derived α-arbutin, a natural compound and (2) compare these findings with bioactively developed liposomes containing α-arbutin utilizing the B16-F10 murine melanoma cell line as a model. Liposomes were obtained through reversed-phase evaporation by applying a spray dryer to assess their stability. The following biologic assays were measured cytotoxicity/antiproliferative (MTT, Neutral Red, and dsDNA PicoGreen). In addition, the levels of melanin and purinergic enzymes were also measured. The production of reactive oxygen species (ROS) and nitric oxide (NO) was determined as a measure of oxidative state. Treatment with nano-liposome containing alpha-arbutin induced a significant 68.4% cytotoxicity, similar to the positive control, in the B16-F10 murine melanoma cell line at 72 hr. Further, arbutin and liposomes containing alpha-arbutin increased levels of ROS and nitrite formation at 72 hr at the highest concentration (100 and 300 µg/ml) of treatments. Arbutin and liposomes containing alpha-arbutin reduced melanin levels at all tested concentrations. In addition, arbutin and alpha-arbutin containing liposomes lowered nucleotides (AMP, ADP, and ATP) and nucleoside (adenosine) levels in melanoma cells. Evidence suggests that α-arbutin containing liposome can be considered as an alternative immunosuppressive agent stimulated in melanoma treatment.

Phyto-cytogenotoxic potential assessment of two medicinal plants: Davilla nitida (Vahl) Kubitzki and Davilla elliptica (A. St.-Hill) (Dilleniaceae).

Humans have been using plants in the treatment of various diseases for millennia. Currently, even with allopathic medicines available, numerous populations globally still use plants for therapeutic purposes. Although plants constitute a safer alternative compared to synthetic agents, it is well established that medicinal plants might also exert adverse effects. Thus, the present investigation aimed to assess the phytotoxic, cytotoxic, and genotoxic potential of two plants from the Brazilian Cerrado used in popular medicine, Davilla nitida (Vahl) Kubitzki, and Davilla elliptica (A. St.-Hil.). To this end, germination, growth, and cell cycle analyses were conducted using the plant model Lactuca sativa. Seeds and roots were treated with 0.0625 to 1 g/L for 48 hr under controlled conditions. The germination test demonstrated significant phytotoxic effects for both species at the highest concentrations tested, while none of the extracts produced significant effects in the lettuce growth test. In the microscopic analyses, the aneugenic and cytotoxic action of D. elliptica was evident. In the case of D. nitida greater clastogenic action and induction of micronuclei, (MN) were noted suggesting that the damage initiated by exposure to these extracts was not repaired or led to apoptosis. These findings indicated that the observed plant damage was transmitted to the next generation of cells by way of MN. These differences in the action of the two species may not be attributed to qualitative variations in the composition of the extracts as both are similar, but to quantitative differences associated with synergistic and antagonistic interactions between the compounds present in these extracts.

Characterization and Evaluation of the Cytotoxicity of Pregabalin Gels for Oral Application.

The efficacy of pregabalin in pain treatment has led to the search for new formulations for its use through different routes of administration. This study aimed to prepare, characterize, and evaluate the cytotoxicity of pregabalin (PG) gels for topical application in the oral cavity. Solutions with three different concentrations of PG were prepared and added to a 1.0% carbopol gel base. Thermal analyses (TG and DSC) and FTIR were performed on the gel and pure pregabalin. Stability (preliminary and accelerated) and rheology studies were also conducted on the gels. Cytotoxicity was evaluated in human gingival fibroblasts in the following groups: WG (1.0% carbopol gel base), PG2G (2.0% pregabalin gel), PG5G (5.0% pregabalin gel), and PG10G (10% pregabalin gel). A transparent and homogeneous gel with a pH of 6 was obtained. The formulations showed stability, and the different drug concentrations did not influence the product's characteristics. None of the tested groups showed cytotoxicity for the analyzed cells. The pregabalin gels exhibited favorable and non-toxic characteristics for human gingival fibroblasts in vitro. Therefore, this product may be a promising therapeutic alternative for topical application in the oral mucosa.

Comprehensive Analysis of Kisspeptin Signaling: Effects on Cellular Dynamics in Cervical Cancer.

Kisspeptin, a key neuropeptide derived from the KISS1R gene, is renowned for its critical role in regulating the hypothalamic-pituitary-gonadal axis and reproductive hormone secretion. Beyond its primary function in reproductive biology, emerging research has illuminated its influence in various cancers, mediating significant effects through its interaction with the G protein-coupled receptor, kisspeptin receptor. This interaction has been implicated in modulating cellular processes such as proliferation and metastasis, making it a potential target for therapeutic intervention. Our study initially screened ten kisspeptin-10 analogs through cytotoxic effects of kisspeptin-10 (KP10) and its analogs in several cancer types, including cervical, prostate, breast, and gastric cancers, with a particular focus on cervical cancer, where the most profound effects were observed. Further exploration using kinase array assays revealed that these analogs specifically alter key kinases involved in cancer progression. Migration assays demonstrated a substantial decrease in cell motility, and Bioluminescence Resonance Energy Transfer assays confirmed these analogs' strong interactions with the kisspeptin receptor. Overall, our results indicate that these KP10 analogs not only hinder cervical cancer cell proliferation but also curtail migration through targeted modulation of kinase signaling, suggesting their potential as therapeutic agents in managing cervical cancer progression. This comprehensive approach underscores the therapeutic promise of exploiting kisspeptin signaling in cancer treatment strategies.

Phenanthroline and phenyl carboxylate mixed ligand copper complexes in developing drugs to treat cancer.

The success of a classic inorganic coordination compound, Cisplatin, cis-[Pt(NH3)2Cl2], as the first anticancer metallodrug started a field of research dedicated to discovering coordination compounds with antitumor activity, encompassing various metals. Among these, copper complexes have emerged as interesting candidates to develop drugs to treat cancer. In this work, mixed ligand complexes of Cu(II) with diimines (phenanthroline or 4-methylphenanthroline) and 3-(4-hydroxyphenyl)propanoate, phenylcarboxylate or phenylacetate were synthesized. They were characterized in the solid state, including a new crystal structure of [Cu2(3-(4-hydroxyphenyl)propanoate)3(phenanthroline)2]Cl·H2O. The obtained complexes presented a variety of stoichiometries. In solution, complexes were partially dissociated in the corresponding Cu-diimine complex. The complexes bound to the DNA by partial intercalation and groove binding, as assessed by Circular Dichroism, relative viscosity change and UV-Vis titration. The cytotoxicity of the complexes was determined in vitro on MDA-MB-231, MCF-7 (human metastatic breast adenocarcinomas, the first triple negative), MCF-10A (breast nontumoral), A549 (human lung epithelial carcinoma), and MRC-5 (human nontumoral lung epithelial cells), finding an activity higher than that of Cisplatin, although with less selectivity.

Low concentrations of complex mixtures of pesticides and metabolites are toxic to common Carp brain cells (Cyprinus carpio carpio).

Pesticide use increases annually, and Brazil is the world's largest consumer. However, unlike the European Union (EU), there is no established limit value for pesticide mixtures in drinking water, and therefore the concentration of pesticides can reach 3354 times the EU limit. Thus, determining the risk of exposure to pesticide mixtures and their main metabolites is challenging and requires the use of alternative methods. In the present study, the Common Carp Brain (CCB) cell line was used to evaluate the in vitro toxicity of relevant pesticide mixtures (glyphosate, 2,4-D, atrazine, and mancozeb) and their main metabolites after 72 h of exposure. The tested concentrations were based on the Acceptable Daily Intake (ADI) defined by Brazilian legislation. The results showed that cells exposed to lower concentrations of the pesticide mixtures and the pesticide + metabolite mixtures were affected by a decrease in cell confluence, resazurin metabolism, and wound healing capacity. The IBR index showed that lower concentrations had more severe effects, suggesting the absence of safe concentrations of these pesticide and metabolite mixtures for the CCB cell line within the tested concentration range. These findings raise concerns about the effects of exposure to these substances on animal and human health.