A narrative review of cinobufacini for endometrial cancer: mechanisms and therapeutic implications

Advanced or recurrent endometrial cancer (EC) faces limited therapeutic options and frequent chemoresistance. Cinobufacini, a traditional Chinese medicine extract derived from the dried skin of Bufo bufo gargarizans Cantor, contains bufadienolides (including cinobufagin, bufalin, and cinobufotalin) as its core antitumor active constituents and exhibits broad-spectrum antitumor activity in multiple cancers. However, direct evidence in EC is limited. Its multitarget actions suggest potential applicability to EC. This study aimed to systematically elucidate the antitumor effects and molecular mechanisms of cinobufacini against EC and provide a theoretical basis for its clinical translation.

A literature search was performed in PubMed, China National Knowledge Infrastructure (CNKI), and Elsevier using terms including "Cinobufacini", "cinobufagin", "toad venom", "anti cancer", "cancer", "endometrial cancer", and "molecular mechanism". Evidence on cinobufacini's anticancer mechanisms in other tumors was correlated with key molecular features of EC.

Cinobufacini's multitarget actions-inducing cell death and inhibiting proliferation-may counteract EC hallmarks such as phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK), and hormone receptor pathway alterations, and could help overcome chemoresistance. However, direct preclinical and clinical data on EC are absent; rigorous in vitro and in vivo validation is needed.

Cinobufacini is a promising candidate for EC based on its established multitarget mechanisms in other cancers. This review offers a mechanistic rationale and framework for future EC-specific studies to enable clinical translation.