Potential antitumor activity of triptolide and its derivatives: Focused on gynecological and breast cancers

Cancer remains one of the greatest global health concerns. This is especially true for gynecological cancers, which include cervical, ovarian, and endometrial cancers, and breast cancer. Natural products used for cancer treatment offer some unique advantages. Triptolide (TPL) is a biologically active terpenoid extracted from Tripterygium wilfordii, which exhibits anti-inflammatory, immunosuppressive, antitumor, and other pharmacological activities. However, clinical applications of TPL are restricted because of poor water solubility and severe cytotoxicity; to overcome these limitations, various TPL derivatives and drug delivery systems, especially nanocarriers, have been used. Furthermore, various preclinical and clinical studies have demonstrated that TPL and its derivatives exhibit excellent antitumor effects by targeting proteins involved in multiple signaling pathways. Here, we review the progress regarding novel drug delivery systems, antitumor activities, and molecular mechanisms of action of TPL and its derivatives against gynecological and breast cancers. TPL and its derivatives inhibit tumor growth, suppress tumor metastasis, and enhance the drug sensitization of resistant cancers. In addition, TPL and its derivatives exert synergistic antitumor effects against gynecological and breast cancers when combined with existing antitumor drugs, such as carboplatin, cisplatin, and PI3K inhibitors. Moreover, we highlight the clinical potential of TPL analogs against cancer from bench to bedside and their prospects for future applications in gynecologic and breast cancers.