Silymarin in cancer therapy: Mechanisms of action, protective roles in chemotherapy-induced toxicity, and nanoformulations
Yin Wang, Ai-Jun Yuan, Yuejin Wu, Limei Wu, Ling Zhang
Abstract
Silymarin, a milk thistle extract, has anti-inflammatory, immunomodulatory, anti-lipid peroxidative, anti-fibrotic, anti-oxidative, and anti-proliferative properties. Silymarin exhibits not only anti-cancer functions through modulating various hallmarks of cancer, including cell cycle, metastasis, angiogenesis, apoptosis, and autophagy, by targeting a plethora of molecules, but also plays protective roles against chemotherapy-induced toxicity, such as nephrotoxicity, hepatotoxicity, cardiotoxicity, and neurotoxicity. One of the problems of silymarin in (pre)clinical studies is its poor water solubility, leading to low intestinal absorption and, therefore, low bioavailability. To address these challenges, silymarin nanoformulations have emerged with added benefits, including excellent drug loading, sustained release, improved cellular uptake, and targeting tumor cells. Besides the chemical and biological properties, here we summarized the anti-cancer functions and the mechanism of action of silymarin in both free form and nanoformulations and its protective roles against chemotherapy-induced toxicity.