The Effects of NT-1044, a Novel AMPK Activator, on Endometrial Cancer Cell Proliferation, Apoptosis, Cell Stress and In Vivo Tumor Growth

• DOI: 10.3389/fonc.2021.690435
• Publication Date: 2021-08-05T13:42:22Z
• Authors: Dario R. Roque; Lu Zhang; Weiya Z. Wysham; Jianjun Han; Wenchuan Sun; Yajie Yin; James N. Livingston; Ken W. Batchelor; Chunxiao Zhou; Victoria L. Bae-Jump
• Keywords: 2. Zero hunger; 0301 basic medicine; obesity; 03 medical and health sciences; Oncology; proliferation; endometrial cancer; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; metformin; NT-1044; RC254-282; 3. Good health

Objectives Anti-diabetic biguanide drugs such as metformin may have anti-tumorigenic effects by behaving AMPK activators and mTOR inhibitors. Metformin requires organic cation transporters (OCTs) for entry into cells, NT-1044 is an activator designed to greater affinity two of these transporters, OCT1 OCT3. We sought compare the on cell proliferation in human endometrial cancer (EC) lines tumor growth endometrioid EC mouse model. Methods Cell was assessed lines, ECC-1 Ishikawa, MTT assay after exposure 72 hours treatment. Apoptosis analyzed Annexin V-FITC cleaved caspase 3 assays. cycle progression evaluated Cellometer. Reactive oxygen species (ROS) were measured using DCFH-DA JC-1 For vivo studies, we utilized LKB1 fl/fl p53 model cancer. The mice treated with placebo or following onset 4 weeks. Results significantly inhibited a dose-dependent manner both (IC50 218 μM Ishikawa; 87 cells). Treatment resulted G1 arrest, induced apoptosis increased ROS production lines. phosphorylation decreased S6, key downstream target pathway. Expression proteins CDK4, CDK6 cyclin D1 fashion while cellular stress protein expression As compared placebo, obese lean mice. Conclusions suppressed through induction stress, activation inhibition In addition, under conditions. More work needed determine if this novel will be beneficial treatment women EC, disease strongly impacted obesity diabetes.