Metabolic reprogramming, especially the dysregulation of glutamine metabolism, is pivotal in tumorigenesis and resistance to therapy. Elevated glutamine metabolic pathways were observed in patients with primary DLBCL. However, the glutamine derivative, alpha-ketoglutarate (α-KG), acted against DLBCL’s invasiveness. Using DM-αKG, a form of α-KG that can permeate cells, significantly curtailed tumour growth by triggering both apoptotic and non-apoptotic cell death, linked to increased oxidative stress in lymphoma cells. This highlights α-KG’s potential as a therapeutic approach for DLBCL, particularly for those with the aggressive double-hit lymphoma (DHL) variant.
Key takeaways: α-KG inhibits tumor growth of diffuse large B-cell lymphoma by inducing ROS and TP53-mediated ferroptosis
- Metabolic reprogramming’s role: Dysregulation of glutamine metabolism, a form of metabolic reprogramming, is crucial in tumorigenesis. Understanding these metabolic shifts can provide insights into ageing and cellular health
- α-KG’s potential: The glutamine derivative, alpha-ketoglutarate (α-KG), has shown promise in counteracting the invasiveness of DLBCL, a type of lymphoma. This suggests that α-KG or similar compounds might have broader applications in promoting cellular health and longevity
- Oxidative stress: The use of α-KG led to increased oxidative stress in lymphoma cells, resulting in cell death. Oxidative stress is a key factor in ageing, and understanding how compounds like α-KG influence it can be pivotal for longevity research
Reference: Cai, Y. et al. “α-KG inhibits tumor growth of diffuse large B-cell lymphoma by inducing ROS and TP53-mediated ferroptosis.” Cell Death Discovery, vol. 9, no. 1, 2023, p. 182, doi: 10.1038/s41420-023-01475-1.