Investigation of the anticancer effect of newly synthesized palladium conjugate Schiff base metal complexes on non-small cell lung cancer cell line and mouse embryonic fibroblast cell line.

Lung cancer remains one of the leading causes of death worldwide. Due to the side effects of chemotherapeutic agents on normal cells and the development of resistance by cancer cells, there is an urgent need for alternative new pharmacological agents. Palladium (Pd)-conjugated Schiff base (SB) compounds represent an alternative approach with promising potential applications in cancer treatment. This study aims to identify novel therapeutic agents on A549 cells through the synthesis and characterization of Schiff base conjugated-Palladium complexes (Pd-L1 and Pd-L2). Additionally, it seeks to elucidate the mechanism of action of these compounds on both the A549 and NIH/3T3 cell lines. In the present study, two new Pd-L1 and Pd-L2 were synthesized for the first time and characterized mainly by single crystal X-ray diffraction and 1H, 13C, 31P NMR techniques. The cytotoxic effect of the compounds was evaluated by MTT assay on A549 and NIH/3T3 cell lines for 24 and 48 h. Cisplatin was used as a positive control group. Based on the cytotoxicity results, the complexes were evaluated for their anticancer activities against A549 cell lines for 48 h through reactive oxygen species (ROS), cell cycle, apoptotic, and necrotic cell analyses. The most potent cytotoxic effects were determined for Pd-L1 (IC50: 23.33 µM), Pd-L2 (IC50: 3.19 µM), and cisplatin (IC50: 33.27 µM) on A549 cells (p < 0.05). The compounds exhibited a significant cytotoxic effect at lower concentrations on A549 cells compared to NIH/3T3 cells (p < 0.05). All compounds showed a significant increase in ROS levels in A549 cells compared to the control group (p < 0.05). While necrosis and apoptosis was observed in A549 cells treated with cisplatin, induction of apoptosis was effective in cell death for A549 cells treated with Pd-L1 and Pd-L2 (p < 0.05). Additionally, it was observed that the compounds inhibited cell proliferation in the G0/G1 and G2/M cell cycle phases (p < 0.05). All compounds induced cell cycle arrest and cell death in A549 cells by increasing ROS levels. The results obtained in the present study could advance the utilization of the compounds as anticancer agents.

Okadaic Acid-Induced Alzheimer's in Rat Brain: Phytochemical Cucurbitacin E Contributes to Memory Gain by Reducing TAU Protein Accumulation.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive memory loss and cognitive decline, with hallmark pathologies related to amyloid beta (Aß) and TAU. Natural phytochemicals show promise for drug discovery to fill the current therapeutic innovation gap in AD. This study investigated the effect of cucurbitacin E (CuE), one of the bioactive components of Ecballium elaterium, on TAU fibril formation in okadaic acid-induced AD in rats. In a randomized design, we assigned 30 female Sprague Dawley rats to one of five experimental groups: (1) control, (2) stereotaxic surgery, (3) stereotaxic surgery + artificial cerebrospinal fluid, (4) stereotaxic surgery + okadaic acid (AD model), and (5) stereotaxic surgery + okadaic acid + CuE treatment. For experimental groups 4 and 5, rats were administered OKA-ICV (200 ng/kg) followed by CuE (4 mg/[kg·day], intraperitoneally) for 20 days. Expression of the MAPK1/3 and MAPK14 genes associated with TAU metabolism, hippocampal protein levels of these genes, cognitive functions of the rats, and histological accumulation of TAU in the brain were evaluated. Our findings in this preclinical model collectively suggest that phytochemical CuE contributes to memory gain by reducing TAU protein accumulation, which warrants further evaluation in future in vitro and in vivo studies.