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.
Citations
More filters
2 citations
01 Jun 2017
TL;DR: Selenium nanoparticles are cytotoxic to tumor cells and have also been considered as effective carriers for the in vivo targeted delivery of drugs, genetic materials, proteins, and so on and could be used in developing next-generation anticancer agents.
Abstract: The past few years have seen substantial progress in veterinary oncology: new methods have been developed for the diagnosis and treatment of oncological diseases in animals, and the range of possible therapeutic interventions has been broadened. Of interest, in particular, are the prospects for the creation of veterinary pharmaceuticals with the use of various nanoparticles, including colloidal selenium, on the surface of which are immobilized biologically active substances that have antitumor action. Selenium nanoparticles are cytotoxic to tumor cells and have also been considered as effective carriers for the in vivo targeted delivery of drugs, genetic materials, proteins, and so on. The well-tunable polyvalent structures of the selenium nanoparticle surface provide a convenient platform for integrating several therapeutic agents or biomacromolecules with covalent or noncovalent surface conjugation. We synthesized selenium nanoparticles in complex with silymarin, a flavonoid hepatoprotector extracted from the fruit of milk thistle [Silybum marianum (L.) Gaertn.], and we evaluated the cytotoxicity of the resultant preparation to normal and tumorous cells. By using electron microscopy and dynamic light scattering, it was found that the developed procedure ensured the preparation of stable suspensions of silymarin-conjugated selenium nanoparticles with sizes ranging from 20 to 40 nm. The obtained conjugate was shown to be markedly cytotoxic to the Hep-2 tumor cell line, suppressing cell respiration approximately 6.5fold as compared to the control, whereas the respiration of SPEV-2 normal cells was inhibited approximately 2.3-fold. Initial colloidal selenium had much weaker effects on both cell types, and pure silymarin had no statistically significant influence on SPEV-2 cells (in contrast to Hep-2 cells). The results of this study could be used in developing next-generation anticancer agents and are of interest in the implementation of green chemistry-based approaches.
2 citations
Cites background from "Effects and mechanisms of silibinin..."
...In particular, it was shown that silibinin, one of the flavonolignans of Silybum marianum, which currently account for 70 % of the total number of flavonolignans [21], increase in vitro and in vivo Н3 and Н4 histone acetylation in heteroplastid cell line Huh-7 in nude mice [22, 23]....
[...]
Dissertation•
10 Feb 2014
TL;DR: In this paper, the determination of bioactive substance in teas in South Ameri-ca and teas produced from non-traditional sources, especially were studied these herbal teas: Yerba mate, Wira Wira, Muna Muna, Lapacho, Catuaba, Vilcacora, Myrtle lemon, Lemon grass, Milk thistle.
Abstract: Master's thesis deals with the determination of bioactive substance in teas in South Ameri-ca and teas produced from non-traditional sources, especially were studied these herbal teas: Yerba mate, Wira Wira, Muna Muna, Lapacho, Catuaba, Vilcacora, Myrtle lemon, Lemon grass, Milk thistle. In the theoretical part of the thesis is indicated a chemical composition of herbal tea and closer are described types of samples, their botanical charac-teristics, chemical composition, use and health effects. Furthermore, is specified antioxi-dant activity, Polyphenolic compounds and flavonoids. In the practical part are evaluated data of the antioxidant activity, total Polyphenols and flavonoids obtained by laboratory analysis. The-se results are processed in clear charts and graphs and compared with the results given in the literature.
2 citations
Additional excerpts
...Ostropest řec mariánský má regenera ční účinky na jaterní bu ňky poničené alkoholem nebo hepatitidou B a C [192]....
[...]
TL;DR: The genetics, epigenetics factors and role of medicinal plants for the cure of this inimical disease and more in-depth investigations are still required to identify the new drug target and novel therapeutic modalities.
Abstract: Cancer has been a fatal disease since many decades Over the time, it is presented in multiple ways and is a matter of consideration as accounts for the high rate of mortality The aim of the current review was to focus on the genetics, epigenetics factors and role of medicinal plants for the cure of this inimical disease Related articles available in English language (2002-2018) were reviewed with help of different database, including PubMed, Springer Link, Medline, Google Scholar and ScienceDirect In order to ensure credibility and accuracy of data only those articles were considered which are published in indexed journals ie Web of Science and Scopus This project was conducted at the Department of Pharmacy, Government College University, Faisalabad, Pakistan from 02-01-2019 to 28-02-2019 The genetic machinery is vibrantly involved in the interpretation of the signals and is observed to be affected by various dietary factors A sequence of modified activities is observed with use of these dietary elements However, the modification is reviewed through the histone acetyltransferase (HAT), histone deacetylase (HDAC) and DNA methyl transferase (DNMTs), effecting the expression of gene These modified genes, in turn then express the signals in multiple reformed ways Different dietary elements that are used such as polyphenol, alkaloid and flavonoids are effective against cancer The progression of disease involves genetics and epigenetics due to amplification, translocation and mutation during gene expression Though, many studies have been conducted elaborating the role of plants and their ingredients which play a part in inhibition of cancerous cells by blockade of cell cycle and apoptosis; more in-depth investigations are still required to identify the new drug target and novel therapeutic modalities
1 citations
01 Jan 2017
TL;DR: This chapter will explore the evidence base in relation to innovative therapies and technologies that may be useful adjuncts in cancer therapy including hyperthermia, sono photo dynamic therapy (SPDT), circulating tumor cell (CTC) testing, and immunotherapy agent Gc-MAF.
Abstract: Vitamins, minerals and other supplements can be a helpful addition to a diet that may be lacking in some of these elements vital to healthy physiological functioning. There are also intravenous (IV) forms of vitamins which give a much higher dose than what would be possible orally, that have also been found to be beneficial in people living with cancer. Many western herbs have immune boosting and other properties, and may be taken as supplements. Chinese herbal medicine and acupuncture have been used for centuries in the treatment of cancer and its side effects, and are used as an adjunct to orthodox treatment to prevent and alleviate many of the adverse effects associated with surgery, chemotherapy and radiation therapy. Innovative therapies and technologies that may be useful adjuncts in cancer therapy include hyperthermia, sono photo dynamic therapy (SPDT), circulating tumor cell (CTC) testing, and immunotherapy agent Gc-MAF. This chapter will explore the evidence base in relation to these therapies.
1 citations
References
More filters
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 ]...
[...]
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 ]...
[...]
...Hepatocellular carcinoma (HCC) is one of the most common malignancies related to a high mortality globally [1, 2 ]...
[...]
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 ]...
[...]
...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 ]...
[...]
.... Studies have reported that histone acetylation is involved in cell proliferation, differentiation, and cell cycle regulation [ 34 ]...
[...]
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]...
[...]
...and one of the most frequently inactivated genes in malignancies [ 30 , 31]...
[...]
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 ]...
[...]
...Ki-67 is a commonly used biomarker for cell proliferation [ 40 ]...
[...]