The Antitumor Potential of Celastrol: Research Progress on Antitumor Mechanisms and Strategies for Toxicity Reduction with Efficacy Enhancement

Celastrol, a natural compound with potent antitumor activity, has gained considerable attention in drug research and development. Although its use is limited by high toxicity, a narrow therapeutic window, and severe side effects, studies show that celastrol can inhibit tumors through multiple targets and pathways, including by inducing apoptosis, autophagy, as well as suppressing invasion and adhesion. It also enhances antitumor effects by reshaping the immunosuppressive tumor microenvironment, regulating stromal components, and suppressing angiogenesis. This review systematically summarizes recent advances in related research and elaborates on the molecular mechanisms underlying the antitumor activity of celastrol and the key factors contributing to its toxicity. In addition, we further discuss current progress in research focused on reducing celastrol’s toxicity and enhancing its efficacy, aiming to promote its safety and druggability through rational structural modification, target optimization, and advanced formulation development.