Targeting Glutaminolysis to Treat Multiple Myeloma: An In Vitro Evaluation of Glutaminase Inhibitors Telaglenastat and Epigallocatechin-3-gallate.

BACKGROUND: Cancer is associated with metabolic changes from increased cell proliferation and growth. Compared to normal differentiated cells, MM cells use the glycolytic pathway even when adequate oxygen is present triggering "Glutamine addiction". OBJECTIVE: To investigate the single and combined effects of epigallocatechin-3-gallate (EGCG) and telaglenastat, a glutaminase inhibitor, on the proliferation and apoptosis of the multiple myeloma cell line KM3/BTZ. METHODS: KM3/BTZ cells were treated with different concentrations of telaglenastat and EGCG alone or in combination to investigate their effect on proliferation and apoptosis using the CCK8 assay, flow cytometry, and western blotting. The Chou-Talalay combination index analysis was used to explore the effect of telaglenastat combined with EGCG, while the Combination Index (CI) was calculated to analyze whether the combination of the two drugs had a synergistic effect. RESULTS: Telaglenastat and EGCG alone as well as in combination (5 µmol/L telaglenastat + 120 µmol/L EGCG) significantly inhibited the proliferation of KM3/BTZ cells compared to the inhibition effect of the control. Additionally, the combined treatment increased the proportion of KM3/BTZ cells in the G2 phase and decreased the proportion of cells in the G1 phase. The apoptosis rate of EGCG alone and the combined treatment was significantly higher than that of the control group. Bax protein expression was highest in the combined treatment group, whereas Bcl-2 expression was lowest, with the combined treatment group having the highest ratio of Bax/Bcl-2. CONCLUSION: Telaglenastat and EGCG act synergistically to inhibit cell proliferation and promote apoptosis in KM3/BTZ cells, possibly by targeting glutamine metabolism and glycolysis.

Multiple osteolytic primary peripheral T-cell bone lymphoma: the first case report.

Peripheral T-cell lymphoma accounts for about 10% of all cases of non-Hodgkin's lymphoma. However, less than 5% of patients with non-Hodgkin's lymphoma present with hypercalcaemia as the initial symptom, and less than 1% present with primary bone lesions. We herein describe a 76-year-old Chinese man who was diagnosed with primary bone adult T-cell lymphoma with extensive osteolysis, including bone loss in the radius, as the initial manifestation. He had developed severe generalised bone pain and an inability to raise his arms. X-ray examination revealed osteolytic destruction of the forearm with loss of the radial diaphysis. The patient was diagnosed with peripheral T-cell lymphoma based on his immunohistochemical results. He began treatment with the CHOPE chemotherapy regimen, which resulted in significant improvement of his bone pain.