A Promising Natural G6PD Inhibitor for Potential Therapeutic Strategies in DLBCL
Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin lymphoma, has a high degree of clinical and biological heterogeneity. Although most patients can be cured with R-CHOP immunochemotherapy,30-40% of patients have progression or recurrence after treatment. Therefore, there is an urgent need to find new treatments to improve the survival rate of this group of patients. Natural small molecule drugs have unique advantages as anticancer agents due to their low toxicity and multiple targets. This project aims to explore potentially effective natural compounds as new therapeutic strategies for DLBCL. We found that Cinobufagin is a potentially effective therapeutic agent for DLBCL. Glucose 6 phosphate dehydrogenase (G6PD), a risk factor for poor prognosis in DLBCL, was a direct target of Cinobufagin. By inhibiting the enzyme activity of G6PD, Cinobufagin could inhibit DNA synthesis and the production of reductive NADPH, thereby inducing ROS accumulation and apoptosis of DLBCL cells. Our findings provide new strategies for the treatment of DLBCL. Overall design: Effect of 40 nM Cinobufagin treatment for 24h on transcriptome expression of OCI-LY1 cells