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Archive > Volume 32 Issue 8 > 2025,32(8):799-805. DOI:10.3872/j.issn.1007-385X.2025.08.002 Prev Next
Basic Research
Effects of methionine restriction on the proliferation and the pentose phosphate pathway of lung adenocarcinoma cells
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Abstract:
[Abstract] Objective: To investigate the impact of methionine restriction on the proliferation and apoptosis of lung adenocarcinoma (LUAD) cells, and the pentose phosphate pathway. Methods: LUAD cells H1299 and A549 were assigned to the Met+ (100 μmol/L methionine) and Met? (0 μmol/L methionine) groups and cultured continuously for 4 d. Cell counting was used to evaluate the effects of methionine treatment on the proliferation of H1299 and A549 cells. Cell-cycle distribution was detected by PI staining; Cell apoptosis by Annexin Ⅴ-PE/7AAD labeling; intracellular ROS level by DCFH-DA probe; intracellular NADPH and GSH levels by WST-8 and DTNB assays, respectively. The Cancer Genome Atlas (TCGA) was used to analyze the correlations between the expressions of glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) and the methioninemetabolic pathway. WB assay was employed to evaluate the effects of methionine restriction and supplementation of S-adenosylmethionine (SAM), a downstream methionine metabolic product, on the expressions of G6PD and 6PGD, key enzymes in the pentose phosphate pathway, in LUAD cells. Results: Methionine restriction significantly inhibited the proliferation of H1299 and A549 cells (both P < 0.01), arrested cells in G2/M phase (both P < 0.05), elevated total ROS levels (both P < 0.001), and induced apoptosis (both P < 0.001). Furthermore, methionine restriction significantly reduced NADPH and GSH levels (both P < 0.01) and suppressed DNA synthesis (both P < 0.01). TCGA analysis revealed positive correlations between G6PD/6PGD expression levels and the methionine metabolic pathway (both P < 0.001). Methionine restriction down-regulated the expressions of G6PD and 6PGD proteins (both P < 0.01), whereas SAM supplementation partially restored their expressions (both P < 0.01), suggesting that methionine regulated the pentose phosphate pathway through SAM. Conclusion: Methionine restriction suppresses LUAD cell proliferation by inhibiting the PPP, which provides experimental evidence for methionine-restriction therapy for LUAD.
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