Andrographolide in hematological malignancies: potential mechanisms and translational challenges

Hematological malignancies comprise a heterogeneous group of life-threatening diseases arising from the hematopoietic system. Despite substantial advances in immunotherapies and molecularly targeted agents, drug resistance and disease relapse remain formidable clinical challenges. The natural product andrographolide, a diterpenoid lactone isolated from Andrographis paniculata, has attracted increasing research interest for its antitumor potential. This narrative review summarizes and discusses preclinical studies on andrographolide in hematological malignancies, covering its reported antitumor activities, drug synergy, and derivative development. Andrographolide has been reported to trigger intrinsic apoptosis through reactive oxygen species burst, while also suppressing STAT3 signaling via a ROS-dependent mechanism, thereby inducing tumor cell apoptosis. In addition, andrographolide has been reported to induce ferroptosis in a cell context-dependent manner, potentially through regulation of the p38/Nrf2/HO-1 pathway and upregulation of ACSL4 (also known as FACL4) expression; it also exerts anti-proliferative effects through metabolic reprogramming and induction of cellular differentiation. Andrographolide further suppresses inflammatory signaling in malignant cells through blockade of NF-κB signaling. In combination, andrographolide exhibits synergistic effects with cytarabine, vincristine, dexamethasone, and other agents in certain experimental settings. Finally, derivatives and analogs of andrographolide have also been explored.