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Journal ArticleDOI

Effects and mechanisms of silibinin on human hepatoma cell lines.

28 Oct 2007-World Journal of Gastroenterology (Baishideng Publishing Group Inc)-Vol. 13, Iss: 40, pp 5299-5305
TL;DR: It is demonstrated that silibinin significantly reduced the growth of HuH7, HepG2, Hep3B, and PLC/PRF/5 human hepatoma cells and increased acetylation of histone H3 and H4, indicating a possible role of altered histone acetylations in silib inin-reduced HCC cell proliferation.
Abstract: AIM: To investigate in vitro effects and mechanisms of silibinin on hepatocellular carcinoma (HCC) cell growth. METHODS: Human HCC cell lines were treated with different doses of silibinin. The effects of silibinin on HCC cell growth and proliferation, apoptosis, cell cycle progression, histone acetylation, and other related signal transductions were systematically examined. RESULTS: We demonstrated that silibinin significantly reduced the growth of HuH7, HepG2, Hep3B, and PLC/PRF/5 human hepatoma cells. Silibinin-reduced HuH7 cell growth was associated with significantly up-regulated p21/CDK4 and p27/CDK4 complexes, down-regulated Rb-phosphorylation and E2F1/DP1 complex. Silibinin promoted apoptosis of HuH7 cells that was associated with down-regulated survivin and up-regulated activated caspase-3 and -9. Silibinin's anti-angiogenic effects were indicated by down-regulated metalloproteinase-2 (MMP2) and CD34. We found that silibinin-reduced growth of HuH7 cells was associated with increased activity of phosphatase and tensin homolog deleted on chromosome ten (PTEN) and decreased p-Akt production, indicating the role of PTEN/PI3K/Akt pathway in silibinin-mediated anti-HCC effects. We also demonstrated that silibinin increased acetylation of histone H3 and H4 (AC-H3 and AC-H4), indicating a possible role of altered histone acetylation in silibinin-reduced HCC cell proliferation. CONCLUSION: Our results defined silibinin's in vitro anti-HCC effects and possible mechanisms, and provided a rationale to further test silibinin for HCC chemoprevention.

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Citations
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01 Jan 2014
TL;DR: The objective of the current study is to find the sensitivity of lung and breast cancer cell lines against silymarin as observed by the apoptotic gene expression and the associated inhibitory activity of sily marin on the proliferation of both the cell lines.
Abstract: Silymarin, an active extract milk thistle (Silybum marianum) plant, is used for the protection against various liver conditions in both clinical settings and experimental models. Prevailing evidence suggest that the silymarin can prevent the proliferation of cancer cells in both in vivo and in vitro models. It has also been found that silymarin alter the inequality between cell survival and apoptosis by means of interfering with the expressions of cell cycle regulators and proteins involved in apoptosis. Several studies have demonstrated silymarin's anticancer effects by causing cell cycle arrest and inducing apoptosis in different type of cancers. However, there is no report on the comparison of different apoptotic gene expression by the lung and breast cancer cell lines treated with silymarin. The objective of the current study is to find the sensitivity of lung and breast cancer cell lines against silymarin as observed by the apoptotic gene expression and the associated inhibitory activity of silymarin on the proliferation of both the cell lines.

13 citations


Additional excerpts

  • ...Accumulating research evidence caspase-9 [8]....

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Journal ArticleDOI
TL;DR: Results demonstrate that immune responses are effectively induced by a novel fusion protein vaccine targeting beta-hCG, suppressing the growth of hepatocellular carcinoma in mice, and holds promise for the treatment of a number of cancers.

13 citations


Cites background from "Effects and mechanisms of silibinin..."

  • ...One group reported that silibinin hampers angiogenesis via down-regulation of MMP-2 in a couple of hepatocellular carcinoma cell lines [54]....

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Journal ArticleDOI
TL;DR: Silymarin at a low dose can induce cytostatic effect on TW01 cells mainly through an increase of antioxidant-like action, and should be applied carefully to patients with nasopharyngeal carcinoma.
Abstract: Background: Silymarin is an active component from the seeds of Silybum marianum and is widely used as a hepatic protection agent. Apoptosis ind

9 citations

Journal ArticleDOI
TL;DR: The results indicate that silybin revealed a cytoprotective effect when incubated with lasalocid since its cytotoxic impact on HepG2 cells has been significantly diminished.
Abstract: Lasalocid is an ionophore coccidiostatic agent frequently used in poultry. Its extensive use causes the formation of residues in edible tissues and eggs which may pose a risk to consumers. Silybin is the main compound extracted from the herb milk thistle Silybum marianum and its hepatoprotective effect has been reported in literature. The aim of the study was to compare lasalocid and silybin cytotoxic effects followed by their combined use in HepG2 cell line. A cytoprotective effect resulting from the interaction of both pharmacologically active substances was measured. In this study, an MTT test, coomassie brillant blue binding test, and LDH release test determined the effective concentration (EC50) of the compounds. The isobolograms and combination index were used to assess the nature of interaction. The lowest EC50-value for lasalocid was established via the MTT test. This study revealed a lack of silybin cytotoxic effect on the cells. Co-actions of the two drugs led to a significant decrease of lasalocid cytotoxicity. The isobolograms and combination index showed a remarkable antagonistic effect in the course of silybin and lasalocid interaction. The results indicate that silybin revealed a cytoprotective effect when incubated with lasalocid since its cytotoxic impact on HepG2 cells has been significantly diminished.

9 citations

References
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Journal ArticleDOI
28 Mar 1997-Science
TL;DR: The PTEN product has a protein tyrosine phosphatase domain and extensive homology to tensin, a protein that interacts with actin filaments at focal adhesions as discussed by the authors.
Abstract: Mapping of homozygous deletions on human chromosome 10q23 has led to the isolation of a candidate tumor suppressor gene, PTEN, that appears to be mutated at considerable frequency in human cancers. In preliminary screens, mutations of PTEN were detected in 31% (13/42) of glioblastoma cell lines and xenografts, 100% (4/4) of prostate cancer cell lines, 6% (4/65) of breast cancer cell lines and xenografts, and 17% (3/18) of primary glioblastomas. The predicted PTEN product has a protein tyrosine phosphatase domain and extensive homology to tensin, a protein that interacts with actin filaments at focal adhesions. These homologies suggest that PTEN may suppress tumor cell growth by antagonizing protein tyrosine kinases and may regulate tumor cell invasion and metastasis through interactions at focal adhesions.

4,927 citations


"Effects and mechanisms of silibinin..." refers background in this paper

  • .... PTEN is a negative regulator of PI3K-Akt signaling [ 29 ]...

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Journal ArticleDOI
TL;DR: The incidence of hepatocellular carcinoma increased significantly among younger persons (40 to 60 years old) during the period from 1991 to 1995 as compared with earlier periods, and the age-specific incidence of this cancer has progressively shifted toward younger people.
Abstract: Background and Methods Clinical observations have suggested that the number of cases of hepatocellular carcinoma has increased in the United States. We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) data base to determine the age-adjusted incidence of hepatocellular carcinoma from 1976 to 1995, data from the U.S. vital-statistics data base to determine age-adjusted mortality rates from 1981 to 1995, and data from the Department of Veterans Affairs to determine age-adjusted rates of hospitalization for the disease from 1983 to 1997. Results The incidence of histologically proved hepatocellular carcinoma increased from 1.4 per 100,000 population (95 percent confidence interval, 1.3 to 1.4) for the period from 1976 to 1980 to 2.4 per 100,000 (95 percent confidence interval, 2.3 to 2.4) for the period from 1991 to 1995. Among black men, the incidence was 6.1 per 100,000 for the period from 1991 to 1995, and among white men, it was 2.8 per 100,000. There was a 41 percent increase in ...

2,869 citations


"Effects and mechanisms of silibinin..." refers background in this paper

  • .... Recent studies have noted a significant rise in the incidence of HCC in the United States in the past 2 decades [ 2 ]...

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  • ...Hepatocellular carcinoma (HCC) is one of the most common malignancies related to a high mortality globally [1, 2 ]...

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Journal ArticleDOI
25 Sep 1997-Nature
TL;DR: The amino termini of histones extend from the nucleosomal core and are modified by acetyltransferases and deacetylases during the cell cycle, which may direct histone assembly and help regulate the unfolding and activity of genes.
Abstract: 'The amino termini of histones extend from the nucleosomal core and are modified by acetyltransferases and deacetylases during the cell cycle These acetylation patterns may direct histone assembly and help regulate the unfolding and activity of genes

2,846 citations


"Effects and mechanisms of silibinin..." refers background in this paper

  • ...Histone acetylation alters chromatin conformation by m a k i n g p r o m o t e r r e g i o n s m o r e a c c e s s i b l e t o transcription factors and permissive to transcriptional activation [ 34 ]...

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  • ...Histone acetylation modifies nucleosome structure that leads to DNA relaxation, reduces the affinity of histone complexes with DNA, and enhances the access of transcriptional factor to DNA [ 34 ]...

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  • .... Studies have reported that histone acetylation is involved in cell proliferation, differentiation, and cell cycle regulation [ 34 ]...

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Journal ArticleDOI
TL;DR: The results identify a strong candidate tumour suppressor gene at chromosome 10q23.3, whose loss of function appears to be associated with the oncogenesis of multiple human cancers.
Abstract: Deletions involving regions of chromosome 10 occur in the vast majority (> 90%) of human glioblastoma multiformes. A region at chromosome 10q23-24 was implicated to contain a tumour suppressor gene and the identification of homozygous deletions in four glioma cell lines further refined the location. We have identified a gene, designated MMAC1, that spans these deletions and encodes a widely expressed 5.5-kb mRNA. The predicted MMAC1 protein contains sequence motifs with significant homology to the catalytic domain of protein phosphatases and to the cytoskeletal proteins, tensin and auxilin. MMAC1 coding-region mutations were observed in a number of glioma, prostate, kidney and breast carcinoma cell lines or tumour specimens. Our results identify a strong candidate tumour suppressor gene at chromosome 10q23.3, whose loss of function appears to be associated with the oncogenesis of multiple human cancers.

2,777 citations


"Effects and mechanisms of silibinin..." refers background in this paper

  • .... PTEN is a tumor suppressor gene and the deletion or inactivation of this gene has been described in a variety of cancer cell lines [ 30 ,33,53]...

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  • ...and one of the most frequently inactivated genes in malignancies [ 30 , 31]...

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Journal ArticleDOI
TL;DR: Data suggest that in normal tissues and lymphoid neoplasms, PCNA immunolocalization can be used as an index of cell proliferation, however, in some forms of neoplasia, including breast and gastric cancer and in vitro cell lines, the simple relation between PCNA expression and cell proliferation is lost.
Abstract: Proliferating cell nuclear antigen (PCNA) is a 36 kD nuclear protein associated with the cell cycle A monoclonal antibody, PC10, that recognizes a fixation and processing resistant epitope has been used to investigate its tissue distribution Nuclear PCNA immunoreactivity is found in the proliferative compartment of normal tissues PCNA immunoreactivity is induced in lectin stimulated peripheral blood mononuclear cells in parallel with bromodeoxyuridine incorporation and the number of cells with PCNA immunoreactivity is reduced by induction of differentiation in HL60 cells In non-Hodgkin's lymphomas a linear relation between Ki67 and PCNA staining was demonstrated These data suggest that in normal tissues and lymphoid neoplasms, PCNA immunolocalization can be used as an index of cell proliferation However, in some forms of neoplasia, including breast and gastric cancer and in vitro cell lines, the simple relation between PCNA expression and cell proliferation is lost In some breast and pancreatic tumours there is apparent deregulation of PCNA with increased expression in tissues adjacent to the tumours The over-expression in some tumours and in adjacent morphologically normal tissue may represent autocrine or paracrine growth factor influence on PCNA gene expression

1,441 citations


"Effects and mechanisms of silibinin..." refers background or methods in this paper

  • ...Both PCNA and Ki-67 are biomarkers for cell proliferation [ 40 ]...

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  • ...Ki-67 is a commonly used biomarker for cell proliferation [ 40 ]...

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