Silymarin antiproliferative and apoptotic effects: Insights into its clinical impact in various types of cancer

Silymarin is a complex extract isolated from the plant Silybum marianum, widely known for its prominent antioxidant and hepatoprotective effects, although increasing evidences have reported extraordinary antiproliferative and apoptotic abilities. As a result, several signaling pathways involved in cell cycle control, cell proliferation, and cell death have been deconvoluted as critical mechanisms. In this regard, cyclin and cyclin‐dependent pathways have been the most studied ones. Following that, apoptotic pathways, such as p53, Akt, STAT‐3, Ras, and caspases pathways, have been extensively studied, although other mechanisms involved in inflammation and angiogenesis have also been highlighted as silymarin‐likely targets in cancer therapy. Therefore, the main challenge of this review is to discuss the diverse molecular mechanisms for silymarin antiproliferative and apoptotic effects; most of them largely studied in various types of cancers so far. Clinical trials and combination therapies related to silymarin application in cancer prevention and treatment are presented as well.