Multitargeted therapy of cancer by silymarin

Abstract

Silymarin, a flavonolignan from milk thistle (Silybum marianum) plant, is used for the protection against various liver conditions in both clinical settings and experimental models. In this review, we summarize the recent investigations and mechanistic studies regarding possible molecular targets of silymarin for cancer prevention. Number of studies has established the cancer chemopreventive role of silymarin in both in vivo and in vitro models. Silymarin modulates imbalance between cell survival and apoptosis through interference with the expressions of cell cycle regulators and proteins involved in apoptosis. In addition, silymarin also showed anti-inflammatory as well as anti-metastatic activity. Further, the protective effects of silymarin and its major active constituent, silibinin, studied in various tissues, suggest a clinical application in cancer patients as an adjunct to estabilished therapies, to prevent or reduce chemotherapy as well as radiotherapy-induced toxicity. This review focuses on the chemistry and analogues of silymarin, multiple possible molecular mechanisms, in vitro as well as in vivo anticancer activities, and studies on human clinical trials.

Epigenetic modifications and p21-cyclin B1 nexus in anticancer effect of histone deacetylase inhibitors in combination with silibinin on non-small cell lung cancer cells

“…13,20,22,23 Silibinin, a flavonolignan isolated from milk thistle (Silybum marianum) seeds, is well known for its hepatoprotective activity, and is used clinically and as dietary supplement against liver toxicity for decades. 20 Silibinin possesses strong anticancer efficacy against both carcinogen-induced primary lung tumors and chemotherapy resistant lung tumor xenografts, where it decreased tumor incidence, inhibited tumor growth and progression by downregulating inducible nitric oxide synthase and Cox-2 mediated signaling, and overcame NFκB-mediated chemoresistance, respectively. 20,22,23 Additionally, growth inhibitory and pro-apoptotic effects of silibinin were recently observed in NSCLC A549 and H1299 cells.…”

“…20 Silibinin possesses strong anticancer efficacy against both carcinogen-induced primary lung tumors and chemotherapy resistant lung tumor xenografts, where it decreased tumor incidence, inhibited tumor growth and progression by downregulating inducible nitric oxide synthase and Cox-2 mediated signaling, and overcame NFκB-mediated chemoresistance, respectively. 20,22,23 Additionally, growth inhibitory and pro-apoptotic effects of silibinin were recently observed in NSCLC A549 and H1299 cells. 19,25 Mechanistically, silibinin modulated cytokines mediated signaling and induced cell cycle two regions of p21 promoter: region a: -324 to -676 and region b: Sp1/Sp3 binding site +41 to -343.…”

Milk thistle in liver diseases: past, present, future

“…The cancer chemopreventive role of MT flavonolignans has been reported in recent literature (Mazzio and Soliman, 2009 anti-angiogenic and anti-metastatic effects (Ramasamy and Agarwal, 2008). Particularly, the protective effects of silymarin and its major active constituent, silibinin, studied in a variety of in vitro and in vivo cancer models, including liver cancer, suggest that they should be established in therapies as adjuncts in the clinical application in these patients to prevent or reduce chemotherapy as well as radiotherapy-induced toxicity.…”

In Vitro Cancer Research on Ancient Herbal Remedies: A Changing Trend

“…Silymarin is a flavonolignan from S. marianum, which has been found to interfere with cell cycle regulators and apoptotic proteins (Ramasamy and Agarwal, 2008). It inhibits epidermal growth factor receptor (EGFR) signaling along with suppressed expression of cyclindependent kinase (CDK).…”

“…The presence of silymarin leads to apoptosis through the mitogen-activated protein kinase (MAPK)/C-JUN N-terminal kinase (JNK) pathway. Silibinin, the most active compound of silymarin, has been shown to interfere with metastasis (Ramasamy and Agarwal, 2008;Kim et al, 2009). …”