Unveiling Gambogenic acid as a promising antitumor compound: A review.

Gambogenic acid (GNA) is a derivative of gambogic acid (GA), a polyprenylated xanthone isolated from Garcinia hanburyi. Compared with the more widely studied GA, GNA has demonstrated advantages such as a more potent antitumor effect and less systemic toxicity than GA according to early investigations. Therefore, the present review summarizes the effectiveness and mechanisms of GNA in different cancers and highlights the mechanisms of action. In addition, drug delivery systems to improve the bioavailability of GNA and its pharmacokinetic profile are included. GNA has been applied to treat a wide range of cancers, such as lung, liver, colorectal, breast, gastric, bladder and prostate cancers. GNA exerts its antitumor effects as a novel class of enhancer of zeste homolog 2 (EZH2) inhibitors. It prevents cancer cell proliferation by inducing apoptosis, ferroptosis, and necroptosis and controlling the cell cycle as well as autophagy. GNA also hinders tumor cell invasion and metastasis by downregulating metastasis-related proteins. Moreover, GNA increases the sensitivity of cancer cells to chemotherapy and has shown effects on multidrug resistance in malignancy. This paper is helpful for the prevention and treatment of cancers using GNA.