Cardamonin as a potential anticancer agent: Preclinical insights and clinical implications

Abstract

Cardamonin is a natural chalcone that has been extensively investigated for its anticancer activity. However, its clinical relevance is still not explicit, limiting its progression into clinical trials and highlighting a persistent gap between preclinical evidence and practical application. This review aims to assess the readiness of cardamonin to progress from laboratory research to clinical application as an anticancer agent by examining both scientific evidence and translational challenges. Preclinical pharmacokinetic and pharmacodynamic data suggest that cardamonin’s therapeutic potential as an anticancer agent is hindered by its poor oral bioavailability. Although its molecular targets remain undefined, evidence indicates that cardamonin can inhibit various signaling pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells, mammalian target of rapamycin, signal transducer and activator of transcription 3, and Wnt/β-catenin. The lack of in vivo toxicity studies creates uncertainty regarding the balance between its therapeutic benefits and potential adverse effects when moving from laboratory research to human trials. Despite these limitations, cardamonin has, however, demonstrated antiproliferative, anti-metastatic, and chemosensitizing effects, mainly against breast, colorectal, and ovarian cancers. Nevertheless, exploring its combination with standard chemotherapeutic agents may offer a promising foundation for advancing cardamonin into clinical trials.

Keywords: Cardamonin; Pharmacodynamics; Pharmacokinetics; Chalcones; Flavonoids; Anticancer; Preclinical studies

Core Tip: This review summarizes preclinical studies on cardamonin, highlighting that pharmacokinetic studies show poor oral bioavailability, whereas pharmacodynamic findings demonstrate its antiproliferative, anti-metastatic, and chemosensitizing effects, primarily through inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells, mammalian target of rapamycin, signal transducer and activator of transcription 3, and Wnt/β-catenin signaling pathways. However, the limited in vivo toxicity data raise concerns about the balance between cardamonin’s therapeutic potential and safety, posing challenges for its translation from preclinical research to clinical application.