Andrographolide inhibits Burkitt's lymphoma by binding JUN and CASP3 proteins.

ABSTRACT

BACKGROUND: Burkitt's lymphoma, one of the most common subtypes of pediatric malignant lymphoma, is notorious for its swift onset, aggressive proliferation, pronounced invasiveness, and marked malignancy. The therapeutic landscape for Burkitt's lymphoma currently falls short of providing universally effective and tolerable solutions. Andrographolide, a primary active component of Andrographis paniculata, is renowned for its properties of heat-clearing, detoxification, inflammation reduction, and pain relief. It is predominantly used in treating bacterial and viral infections of the upper respiratory tract, as well as dysentery. Various reports highlight the antitumor effects of andrographolide. Yet, its specific impact and the underlying mechanism of action on Burkitt's lymphoma remain an uncharted area of research. METHOD: We employed network pharmacology to pinpoint the targets of andrographolide's action on Burkitt's lymphoma and the associated pathways. We then evaluated the impact of andrographolide on Burkitt's lymphoma using both in vitro and in vivo patient-derived xenograft (PDX) models. Concurrently, we confirmed the molecular targets of andrographolide in Burkitt's lymphoma through immunofluorescence assays. RESULT: Utilizing network pharmacology, we identified 15 relevant targets, 60 interrelationships between these targets, and numerous associated signaling pathways for andrographolide's action on Burkitt's lymphoma. In vitro efficacy tests using High-throughput Drug Sensitivity Testing and in vivo PDX model evaluations revealed that andrographolide effectively curtailed the growth of Burkitt's lymphoma. Moreover, we observed a increased in the expression of JUN (c-Jun) and CASP3 (Caspase 3) proteins in Burkitt's lymphoma cells treated with andrographolide. CONCLUSION: Andrographolide inhibits the growth of Burkitt's lymphoma by inhibiting JUN and CASP3 proteins.