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