Molecular Mechanisms of Silibinin-Mediated Cancer Chemoprevention with Major Emphasis on Prostate Cancer

Abstract

Abstract. Despite advances in early detection, prostate cancer remains the second highest cancer mortality in American men, and even successful interventions are associated with enormous health care costs as well as prolonged deleterious effects on quality of patient life. Prostate cancer chemoprevention is one potential avenue to alleviate these burdens. It is a regime whereby long-term treatments are intended to prevent or arrest cancer development, in contrast to more direct intervention upon disease diagnosis. Based on this intention, cancer chemoprevention generally focuses on the use of nontoxic chemical agents which are well-tolerated for prolonged usage that is necessary to address prostate cancer's multistage and lengthy period of progression. One such nontoxic natural agent is the flavonoid silibinin, derived from the milk thistle plant (Silybum marianum), which has ancient medicinal usage and potent antioxidant activity. Based on these properties, silibinin has been investigated in a host of cancer models where it exhibits broad-spectrum efficacy against cancer progression both in vitro and in vivo without noticeable toxicity. Specifically in prostate cancer models, silibinin has shown the ability to modulate cell signaling, proliferation, apoptosis, epithelial to mesenchymal transition, invasion, metastasis, and angiogenesis, which taken together provides strong support for silibinin as a candidate prostate cancer chemopreventive agent.

Silibinin attenuates methotrexate-induced pulmonary injury by targeting oxidative stress

“…The compound is known to exhibit antioxidative activity, which has been previously reported to result in a number of biologically protective effects, including anti-inflammatory, antitumor and hepatoprotective effects (10)(11)(12)(13). Silibinin has been demonstrated to be a potent antioxidant, supporting the capacity of cellular antioxidative agents, such as glutathione (GSH) and superoxide dismutase (SOD), to target reactive oxygen species.…”

Silibinin Combination with Arsenic Strongly Inhibits Survival and Invasiveness of Human Prostate Carcinoma Cells

“…Silibinin causes G1 arrest by downregulation of cyclin D1 and E, CDK2, -4, and -6, and upregulation of cyclin-dependent kinase inhibitors including p21 and p27 (14). Arsenic affects cell cycle regulatory proteins of G2/M phase in cancer cells (36).…”

“…Further, silibinin is known to decrease the PSA levels and inhibit the functions of AR in hormone responsive prostate cancer cells. Silibinin targets a number of signaling pathways regulating cell cycle, apoptosis, angiogenesis, and metastasis in PCa cells (14). Silibinin initiated an apoptotic response triggered by ROS generation and then imposed energy restrictions to induce autophagic death (15).…”

Emerging potential of natural products for targeting mucins for therapy against inflammation and cancer

“…Silibinin, a naturally occurring polyphenolic antioxidant, is a major constituent of the dietary supplement milk thistle ( Silybum marianum L.) extract and has been extensively studied for anti-inflammatory and anti-neoplastic effects [120]. In airway epithelial cells, silibinin was demonstrated to inhibit mucin production and secretion.…”