In this study, several etodolac‐based hydrazone, thiazolidinone, and triazole derivatives that we synthesized and characterized in our earlier research were tested against the hormone‐responsive breast cell line MCF‐7 and the triple‐negative MDA‐MB‐231, as well as the murine origin fibroblast cell line L‐929, at varying doses for their effects on cell viability and toxicity and for their inhibitory activity on cyclooxygenase‐2 (COX‐2)/prostaglandin E2 (PGE2) formation. Cell viability and apoptosis tests were utilized to assess the anti‐cancer potential of etodolac and its derivatives after the cells were exposed to varied concentrations of synthesized compounds for three different time periods. ELISA and Western blot methods were used to detect protein levels. All synthesized compounds demonstrated higher anti‐cancer activity at significantly lower doses compared to etodolac (half‐maximal inhibitory concentration [IC50] of 0‐50 µM range in derivatives versus 0.5−1 mM range in etodolac). Except for SGK 242, which had a major toxic effect on all cells, the chemicals SGK 206 and SGK 217 had a twice‐less impact on control murine L‐929 fibroblasts. Similar to proliferation, low concentrations of SGK 206 and SGK 217 (25−50 µM) significantly induced apoptosis in breast cancer cells but not in normal cells. Additionally, they inhibited COX‐2 protein expression at 50 µM, and SGK 206 inhibited PGE2 release more effectively than etodolac in cancer cells. The results of this study suggest that, in comparison to a healthy control group, the thiazolidinone derivative SGK 206 and the thiazolidinone derivative SGK 217 are more effective than etodolac when it comes to the breast cancer cell lines MCF‐7 and MDA‐MB‐231. SGK 206 exhibits a low IC50 value, a distinct dose–response relationship, and strong apoptotic effects, particularly on MDA‐MB‐231 cells.

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs), which are commonly used for their anti-inflammatory and analgesic properties, have also been found to prevent cancer. (±)(R,S) Etodolac is an NSAID that belongs to the class of cyclooxygenase-2 inhibitors. Various derivatives of etodolac are synthesized to boost its anti-proliferative action and lessen its potential negative effects. In our earlier studies, some novel derivatives of etodolac exhibited stronger cytotoxic effects on prostate cell lines and had similar effects on leukemia cells in pre-screening experiments. Objective: Using the K562 leukemia cell line as a model, we sought to investigate the anti-cancer properties of a hydrazide-hydrozone derivative (SGK-205) and a 4-thiazolidinone derivative of etodolac (SGK-216). Materials and Methods: In the current investigation, SGK-205 and SGK-216 compounds were administered to K562 cells for 24 and 48 hours at concentrations of 10, 25, 50, 75 and 100 μM. Cell viability was assessed using the MTT test, and apoptosis by Annexin V-PI staining and mitochondrial membrane potential assays, together with mRNA expressions of apoptotic proteins. The levels of the proteins, HER2 and COX2, were also examined to evaluate COX2 inhibitory capacity. Results: In K562 cells, there was a definite dose-dependent response to SGK-205 and SGK-216 compounds. Results from MTT viability tests, together with mitochondrial membrane potential measurements and Annexin V-PI staining, revealed that SGK-216 and SGK-205 significantly outperformed etodolac in terms of their apoptotic and anti-proliferative activities. The concentration range of 10-20 M for both chemicals was sufficient to start biological responses. Apoptosis was also investigated through the expressions of pro- and anti-apoptotic proteins. Additionally, gene expression research demonstrated SGK-205 to be a beneficial substitute to etodolac in lowering COX-2 and human epidermal growth factor receptor-2 (HER2) expression. Conclusion: Our data indicated both derivatives to have higher anti-proliferative and apoptotic effects compared to etodolac. An overall assessment highlighting apoptotic induction potential, acceptable toxicity levels, a consistent dose-response relationship, and COX2 inhibitory actions, in particular, indicated SGK-205 as a viable novel therapeutic.

Objective: The aim of this study was to reveal the effect of apocynin (APO) on the factors involved in obesity-related endothelial dysfunction (ED) and atherosclerosis (AS). Materials and Methods: Male Wistar albino rats were divided into control (CNT), high-fat diet (HFD) and HFD+APO groups. HFD and HFD+APO groups were fed HFD for sixteen weeks. APO (25 mg/kg) was administered to the HFD+APO group for the last four weeks. The effects of APO on: AS-related metabolic parameters (triglyceride, total cholesterol, high-density lipoprotein-cholesterol, insulin and leptin), oxidative stress (OS), [ malondialdehyde, glutathione, nicotinamide adenine dinucleotide phosphate (NADPH)- oxidase-2, oxidised-low-density lipoprotein (ox-LDL) and 8-hydroxy-2-deoxyguanosine], low-density lipoprotein and ox-LDL uptake potential (activin receptor-like kinase-1 and lectin-like oxidized low-density lipoprotein receptor-1, respectively), tissue inflammation (myeloperoxidase, monocyte-chemoattractant-protein-1, tumor necrosis factor-alpha), ED (endothelial-nitric oxide synthase, inducible-nitric oxide synthase, nitric oxide), programmed cell death (terminal deoxynucleotidyl-transferase-dUTP-nick-end labeling, cleaved-poly-ADP-ribose-polymerase, gasdermin-D N-terminal fragment, caspase-1), smooth muscle cell transformation (alpha-smooth muscle actin), histology and ultrastructure of thoracic aorta were evaluated. Results: In obesity, APO had an ameliorative effect on metabolic parameters, OS, inflammation, ED, programmed cell death and ox- LDL uptake potential, but not on foam cell formation and LDL uptake potential. Conclusion: Apocynin may improve ED and AS in obesity by suppressing OS-linked factors involved in the early stage of AS.

Urtica dioica (stinging nettle) is an herb commonly in use as a medical supplement for its anticarcinogenic, antiinflammatory, analgesic, antifungal . In this study, phytochemical composition extract was analyzed and its apoptotic and antiproliferative effects were investigated in K562 cell line, a model cell line for chronic myeloid leukemia (CML). K562 cells exposed to different concentrations of Urtica dioica extract (0, 25, 50, 75 and 100 mg/ml) were tested for cell proliferation and appropriate methods and different phases of the cell cycle were analyzed using flow cytometry. Phenolic content of the plant was analyzed by LC–MS/MS. We showed that Urtica dioica ethanol extract has four phenolic compounds: caffeic acid, chlorogenic acid (major compound), malic acid and rutin. Urtica dioica significantly repressed proliferation of K562 cells compared to control mononuclear cells (PBMCs) isolated from the peripheral blood of healthy donors. Increase in Bax/Bcl-2 and PARP cleavage ratio, decrease in mitochondrial membrane potential indicated that the extract inhibited cell proliferation through an apoptosis-mediated process. Furthermore, cell cycle arrest at G0/G1 phase increased in a concentration dependent manner. Our results explicitly demonstrate that ethanol extract of to decrease in cell viability and proliferation, initiate apoptosis and induces G0/G1 cell cycle accumulation in this cell line. This study is the first to show antiproliferative and apoptotic effects of Urtica dioica on leukemia cell line in vitro.

Background. Pancreatic ductal adenocarcinoma remains difficult to treat and has an exceptionally poor prognosis. While prior studies have noted antitumour properties for midazolam in pancreatic cancer, whether this response involves developmental signaling pathways is unclear. Here, we evaluated midazolam-treated MIA PaCa-2 cells to identify associated Wnt and Hedgehog transcriptional shifts and their systems-level context. Methods. MIA PaCa-2 cells were exposed to midazolam (20–100 µM) for 24 h. We measured metabolic viability by MTT and apoptosis by Annexin V-FITC/7-AAD flow cytometry at 60 µM. Expression of 18 targeted genes was quantified by RT-qPCR using ACTB for normalization. Changed genes were examined through STRING/KEGG networks, TCGA-PAAD survival analysis, DGIdb annotations, and preliminary FZD7 molecular docking. Results. Midazolam reduced MTT-derived metabolic viability in a concentration-dependent manner (IC₅₀ = 54.6 µM) and significantly increased Annexin V-positive apoptotic populations at 60 µM across three independent experiments. Eight transcripts changed significantly: CTNNB1, TGFBR2, WNT2, WNT7B, HHIP, and DHH declined, while CSNK1A1 and AXIN1 increased (all adjusted p < 0.05). Network analysis highlighted CTNNB1 as the main hub, and high CTNNB1 expression correlated with shorter survival in TCGA-PAAD patients (p = 0.043; HR = 1.58, 95% CI: 1.01–2.47). Conclusions. Midazolam reduced metabolic viability and increased apoptosis in MIA PaCa-2 cells alongside coordinated expression changes in key Wnt and Hedgehog components. Because the required doses far exceed clinical sedation levels and pathway activity was not directly confirmed at the protein level, these findings should be regarded as a preliminary hypothesis rather than evidence of therapeutic efficacy.