The Role of Natural Chalcones and Their Derivatives in Targeting Prostate Cancer: Recent Updates

Prostate cancer (PCa) is the second most prevalent cancer among men and a major cause of cancer-related mortality worldwide. Despite an initial favorable response to hormone-based therapies, many patients ultimately develop an advanced and lethal form of the disease, referred to as castration-resistant PCa (CRPC). CRPC is associated with poor prognosis and a lack of effective curative treatments. As a result, new alternatives or improved therapeutic strategies to combat this life-threatening condition are urgently needed. Chalcones, also referred to as 1,3-diphenyl-2-propen-1-ones, have attracted significant attention because of their potent antitumor properties. Owing to their distinctive chemical structure and diverse biological activities, these compounds are promising candidates for treating various cancers, including PCa. Both naturally occurring and synthetically derived chalcones have demonstrated anticancer potential by modulating key cellular processes, including apoptosis, cell cycle regulation, cell migration, invasion, metastasis and angiogenesis, as well as major signaling pathways, such as PI3K/Akt/mTOR, androgen signaling, and NF-κB. This review aims to outline the recent advances in the therapeutic potential of chalcone derivatives in prostate cancer, with a focus on their molecular targets, mechanisms of action, and translational relevance.