Effects of silibinin on cell growth and invasive properties of a human hepatocellular carcinoma cell line, HepG-2, through inhibition of extracellular signal-regulated kinase 1/2 phosphorylation

Momeny, Majid; Khorramizadeh, Mohammad Reza; Ghaffari, Seyed H.; Yousefi, Mehdi; Yekaninejad, Mir Saeed; Esmaeili, Rezvan; Jahanshiri, Zahra; Noori–Daloii, Mohammad Reza

doi:10.1016/j.ejphar.2008.06.011

Cited by 58 publications

(35 citation statements)

References 60 publications

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“…Silibinin was found to inhibit cell proliferation and invasion in various hepatocarcinoma cell lines (27)(28)(29)(30) as well as in a mouse xenograft model (31). These effects appear to be a consequence of inducing apoptosis as well as cell cycle arrest in hepatocarcinoma cells.…”

Section: Broad Spectrum Cancer Chemopreventive Efficacy Of Silibininmentioning

confidence: 99%

“…These effects appear to be a consequence of inducing apoptosis as well as cell cycle arrest in hepatocarcinoma cells. Silibinin inhibited ERK1/2 signaling, downregulated survivin, highly expressed in cancer protein-1, the E2F1/DP1 complex, cyclin D1, cyclin D3, cyclin E, cyclin-dependent kinase (CDK)2, and CDK4 levels and induced CDK inhibitor (CDKI) Kip1/p27 in hepatocarcinoma HEPG2 cells (27,28). Furthermore, silibinin altered Akt signaling, downregulated phosphorylation of retinoblastoma (Rb), upregulated histone acetylation, and activated caspases 3 and 9 in hepatoma HuH7 cells (30).…”

Section: Broad Spectrum Cancer Chemopreventive Efficacy Of Silibininmentioning

confidence: 99%

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

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Deep

Agarwal

2013

AAPS J

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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.

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Section: Broad Spectrum Cancer Chemopreventive Efficacy Of Silibininmentioning

confidence: 99%

Section: Broad Spectrum Cancer Chemopreventive Efficacy Of Silibininmentioning

confidence: 99%

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

Ting

Deep

Agarwal

2013

AAPS J

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“…Among individuals with advanced HCV-associated liver diseases, an inverse association between silymarin use and progression of liver disease from fibrosis to cirrhosis has been shown [148]. Although no evidence for an effect on clinical outcomes including occurrence of HCC has been demonstrated, antiproliferative action of silymarin on HCC cells has been demonstrated, whose mechanisms include induction of apoptosis by upregulation of proapoptotic proteins including p53, Bax, and caspase-3 [149], modulation of AKT/PTEN [150] and ERK1/2 [151], and cell cycle arrest at G1 and G2 phases [152]. Chemopreventive effects of silymarin have been demonstrated in rodents utilizing HCC models by HBV X transgenic mice [153] and N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis in rats [154].…”

Section: Silymarinmentioning

confidence: 96%

Chemoprevention against hepatocellular carcinoma

Okano

Fujise

Abe

et al. 2011

Clin J Gastroenterol

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Since the majority of hepatocellular carcinoma (HCC) arises from a background of chronic liver diseases caused by infection with hepatitis C virus (HCV) and hepatitis B virus (HBV), chemoprevention targeting patients at high risk of HCC is feasible. In this review article, we summarize current knowledge of chemoprevention against HCC mostly using phytochemicals which have less toxicity than pharmaceutical agents. We describe in vivo and in vitro evidence and proposed mechanisms of beneficial effects of several compounds on the liver, including acyclic retinoid (ACR), angiotensin-converting enzyme inhibitors (ACEIs), caffeine, capsaicin, cepharanthine (CEP), cinnamaldehyde, curcumin, diallyl sulfide (DAS), eicosapentaenoic acid (EPA), epigallocatechin-3-gallate (EGCG), genistein, lycopene, resveratrol, silymarin, sulforaphane (SFN), and xanthohumol (XN). Because antihepatocarcinogenic effects by these compounds are mostly based on experimental studies, clinical evidence is urgently necessary.

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“…Because in our previous study we did not observe a significant effect on HepG2 growth with 25 μM of the drug's concentration (18), in the present study we excluded it, but we included the 100 μM dose in our treatment procedure. The experiments were performed when cells reached 75% confluence and a 24-h synchronization of cell growth was included before the treatments.…”

Section: Cell Lines and Silibinin Treatmentmentioning

confidence: 98%

Multitargeting and Antimetastatic Potentials of Silibinin in Human HepG-2 and PLC/PRF/5 Hepatoma Cells

Ghasemi¹,

Ghaffari²,

Momeny³

et al. 2013

Nutrition and Cancer

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Hepatocellular carcinoma (HCC) is the most common sort of primary liver malignancy with poor prognosis. This study aimed at examining the effects of silibinin (a putative antimetastatic agent) on some transcriptional markers mechanistically related to HCC recurrence and metastasis in HepG-2 [hepatitis B virus (HBV)-negative and P53 intact) and PLC/PRF/5 (HBV-positive and P53 mutated) cells. The expression of 27 genes in response to silibinin was evaluated by real-time RT-PCR. The MMP gelatinolytic assay and microculture tetrazolium test (MTT) were tested. Silibinin was capable of suppressing the transcriptional levels of ANGPT2, ATP6L, CAP2, CCR6, CCR7, CLDN-10, cortactin, CXCR4, GLI2, HK2, ID1, KIAA0101, mortalin, PAK1, RHOA, SPINK1, and STMN1 as well as the enzymatic activity of MMP-2 but promoted the transcripts of CREB3L3, DDX3X, and PROX1 in both cells. Some significant differences between the cells in response to silibinin were detected that might be related to the differences of the cells in terms of HBV infection and/or P53 mutation, suggesting the possible influence of silibinin on HCC through biological functions of these 2 prognostic factors. In conclusion, our findings suggest that silibinin could potentially function as a multitargeting antimetastatic agent and might provide new insights for HCC therapy particularly for HBV-related and/or P53-mutated HCCs.

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Effects of silibinin on cell growth and invasive properties of a human hepatocellular carcinoma cell line, HepG-2, through inhibition of extracellular signal-regulated kinase 1/2 phosphorylation

Cited by 58 publications

References 60 publications

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

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

Chemoprevention against hepatocellular carcinoma

Multitargeting and Antimetastatic Potentials of Silibinin in Human HepG-2 and PLC/PRF/5 Hepatoma Cells

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