Anticancer Attributes of Silibinin: Chemo- and Radiosensitization of Cancer

Silymarin, a flavolignan from dried fruit of the milk thistle ( Silybum marianum ) plant, is used as an ancient medicinal plant for protection against various liver disorders. The role of silymarin and its active constituents, mainly silibinin, has been extensively explored and established in the chemopreventive efficacy against different cancers including prostate, lung, stomach, colon, skin, pancreas, and bladder cancer. Its efficacy is accomplished through growth inhibition; cell-cycle arrest through modulation of cyclins, cyclin-dependent kinases, and cyclin-dependent kinase inhibitors; induction of apoptotic cell death; modulation of mitogenic and survival signaling involving MAPK, Akt, EGFR, STAT, NF-κB, and TGF-beta; inhibition of angiogenesis through downregulation of VEGF, iNOS, eNOS, CD31, and HIF-1alpha; reversal of epithelial-mesenchymal transition; and inhibition of invasion and migration. Silibinin, a major constituent of silymarin, has been proved as potential inhibitor of tumor progression and metastasis in preclinical animal models. Silibinin has strong potential as a chemosensitizer and has shown improved efficacy of several chemotherapeutic agents in the treatment and management of cancer with reduced toxicity. The development of resistance to these conventional therapies through induction of prosurvival and mitogenic signaling is reversed by silibinin when combined with chemo- and radiotherapies even at very low doses. Overall, silibinin targets multistep of the carcinogenesis process and improves the therapeutic effects of chemotherapeutic and radiation treatment regimens against cancer with reduced side effects.