Title:Targeting Glutaminolysis to Treat Multiple Myeloma: An In Vitro Evaluation of Glutaminase
Inhibitors Telaglenastat and Epigallocatechin-3-gallate
Volume: 23
Issue: 7
Author(s): Chen Li, Yuhu Feng*, Weiguo Wang, Lingyun Xu, Miao Zhang, Yue Yao, Xiaoqian Wu, Qin Zhang, Wenyue Huang, Xiuxiu Wang, Xue Li, Peipei Ying and Liu Shang
Affiliation:
- Department of Hematology, Fuyang People's Hospital, (The Affiliated Fuyang People’s Hospital of Anhui Medical University),
NO.501, Sanqing Road, Fuyang City, Anhui Province 236000, China
Keywords:
KM3/BTZ cell, EGCG, telaglenastat, cell proliferation, cell apoptosis, multiple myeloma.
Abstract:
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.
