Dual Effects of Silymarin on Nasopharyngeal Carcinoma Cells (NPC-TW01)

Su, Ching‐Hua; Chen, Li‐Jen; Liao, Jyh‐Fei; Cheng, Juei‐Tang

doi:10.1159/000354594

Cited by 9 publications

(7 citation statements)

References 36 publications

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“…Silymarin reduces the incidence of certain cancers [15] . Su et al [16] used silymarin on nasopharyngeal carcinoma cells (NPC-TW01) and found an increase in Bcl-2 expression and a decrease in the activated caspase-3 or apoptosis-inducing factor (AIF) with low-dose (80 μmol/L) treatment.…”

Section: Overviewmentioning

confidence: 99%

Hepatoprotective effect of silymarin

Vargas-Mendoza

Madrigal-Santillán

Morales-González

et al. 2014

WJH

310

171

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The use of medicinal plants in treating illnesses has been reported since ancestral times. In the case of hepatic diseases, several species such as Silybum marianum , Phyllanthus niruri, and Panus giganteus (Berk.) have been shown to ameliorate hepatic lesions. Silymarin is a natural compound derived from the species Silybum marianum , which is commonly known as Milk thistle. This plant contains at least seven flavoligands and the flavonoid taxifolin. The hepatoprotective and antioxidant activity of silymarin is caused by its ability to inhibit the free radicals that are produced from the metabolism of toxic substances such as ethanol, acetaminophen, and carbon tetrachloride. The generation of free radicals is known to damage cellular membranes and cause lipoperoxidation. Silymarin enhances hepatic glutathione and may contribute to the antioxidant defense of the liver. It has also been shown that silymarin increases protein synthesis in hepatocytes by stimulating RNA polymerase I activity. A previous study on humans reported that silymarin treatment caused a slight increase in the survival of patients with cirrhotic alcoholism compared with untreated controls.© 2014 Baishideng Publishing Group Co., Limited. All rights reserved.Key words: Silybum marianum ; Hepatoprotector; Lipoperoxidation; Silymarin Core tip: One of the mechanisms of liver damage caused by alcohol is the generation of free radicals formed by the metabolism of this xenobiotic. Silymarin is an antioxidant that protects the liver from the free radical damage produced by alcohol metabolism. Silymarin is the most used natural compound for the treatment of hepatic diseases worldwide due to its antioxidant, anti-inflammatory, and anti-fibrotic activities. Silymarin functions by stabilizing biological membranes and increasing protein synthesis.

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Section: Overviewmentioning

confidence: 99%

Hepatoprotective effect of silymarin

Vargas-Mendoza

Madrigal-Santillán

Morales-González

et al. 2014

WJH

310

171

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“…The major bioactive compound of silymarin is “silybin” with biological absorption between 20 and 50% . Certain studies have already evidenced the anticancer activity of silymarin on nasopharyngeal carcinoma, prostate cancer, and HCC, yet a detailed investigation of the molecular mechanism is still lacking . The major drawback of silymarin lies in its poor solubility in water, low intestinal absorption, and less bioavailability. , To overcome the hurdle, the new emerging nanoplatform came into the play.…”

Section: Introductionmentioning

confidence: 99%

Silymarin-Loaded, Lactobionic Acid-Conjugated Porous PLGA Nanoparticles Induce Apoptosis in Liver Cancer Cells

Upadhyay

Bhattacharjee

Bhattacharya

et al. 2020

ACS Appl. Bio Mater.

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HepG2 cells (HCC), characterized by epithelial-like morphology, high proliferation rates, and nontumorigenicity, require cost-effective and efficient treatment. Silymarin, a flavonoid extract of Silybum marianum, is effective in the treatment of HCC. Here, we have reported a comparative anticancer study of the well-characterized nanoformulations of lactobionic acid-adorned porous PLGAencapsulated silymarin (LA-PLGA-Sil) with only porous PLGA-encapsulated silymarin (PLGA-Sil) against HepG2 cells. Treatment of HepG2 cells with LA-PLGA-Sil produced a significant deterioration in cell viability at an essentially low dose as compared with PLGA-Sil, due to the adorned lactobionic acid moiety, which results in better targeting. p53, a tumor suppressor gene, essentially initiates apoptosis in cells procuring wild-type p53 (p53 +/+). In our report, treatment of HepG2 cells (p53 +/+) with LA-PLGA-Sil activated p53, which in turn inhibited the proliferation of cells by instigating cell-cycle arrest and apoptosis in a concentration-dependent manner and simultaneously stabilized the nuclear translocation of NFκB-p65. To explore the effect of LA-PLGA-Sil on the expression of microRNA, we observed that LA-PLGA-Sil markedly upregulated the miR-29b in human HCC cells. Reactivation of the p53 gene by miR-29b targeted Bcl-2 and triggered the sequential activation of mediators such as proapoptotic Bax protein, release of cytochrome c, and the activation of caspase proteins (caspase-3 and caspase-9). Furthermore, the overexpression of NFκB-p65 in HepG2 cells reversed the repression, and this stabilization effect of LA-PLGA-Sil on the nuclear translocation of p65 led to the significant downregulation of miR-29b and successively decreased the p53 expression in LA-PLGA-Sil-treated cells, thereby providing a survival mechanism to HepG2. In entirety, our study demonstrated the extensive potential of LA-PLGA-Sil to instigate the cell death of HepG2 cells via apoptosis by targeting the miR-29b/p53 axis through the stabilization of NFκB. It also impaired the migratory activity of HepG2 cells and thereby furnished a comprehensive way to HCC therapeutic treatment.

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“…Box 2. built on references. [420][421][422][423] The dual effects of silymarin can be clearly seen in an experiment by Su et al 424 Here nasopharyngeal carcinoma cells were exposed to low concentrations of silymarin and this showed protumoral effects: "Silymarin increased the expressions of superoxide dismutase 1, catalase, and glutathione peroxidase. Consequently, the cell apoptosis was reduced markedly.…”

Section: Discussionmentioning

confidence: 99%

Role of Silymarin in Cancer Treatment: Facts, Hypotheses, and Questions

Koltai¹,

Fliegel

2022

J Evid Based Complementary Altern Med

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The flavonoid silymarin extracted from the seeds of Sylibum marianum is a mixture of 6 flavolignan isomers. The 3 more important isomers are silybin (or silibinin), silydianin, and silychristin. Silybin is functionally the most active of these compounds. This group of flavonoids has been extensively studied and they have been used as hepato-protective substances for the mushroom Amanita phalloides intoxication and mainly chronic liver diseases such as alcoholic cirrhosis and nonalcoholic fatty liver. Hepatitis C progression is not, or slightly, modified by silymarin. Recently, it has also been proposed for SARS COVID-19 infection therapy. The biochemical and molecular mechanisms of action of these substances in cancer are subjects of ongoing research. Paradoxically, many of its identified actions such as antioxidant, promoter of ribosomal synthesis, and mitochondrial membrane stabilization, may seem protumoral at first sight, however, silymarin compounds have clear anticancer effects. Some of them are: decreasing migration through multiple targeting, decreasing hypoxia inducible factor-1α expression, inducing apoptosis in some malignant cells, and inhibiting promitotic signaling among others. Interestingly, the antitumoral activity of silymarin compounds is limited to malignant cells while the nonmalignant cells seem not to be affected. Furthermore, there is a long history of silymarin use in human diseases without toxicity after prolonged administration. The ample distribution and easy accessibility to milk thistle—the source of silymarin compounds, its over the counter availability, the fact that it is a weed, some controversial issues regarding bioavailability, and being a nutraceutical rather than a drug, has somehow led medical professionals to view its anticancer effects with skepticism. This is a fundamental reason why it never achieved bedside status in cancer treatment. However, in spite of all the antitumoral effects, silymarin actually has dual effects and in some cases such as pancreatic cancer it can promote stemness. This review deals with recent investigations to elucidate the molecular actions of this flavonoid in cancer, and to consider the possibility of repurposing it. Particular attention is dedicated to silymarin's dual role in cancer and to some controversies of its real effectiveness.

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Dual Effects of Silymarin on Nasopharyngeal Carcinoma Cells (NPC-TW01)

Cited by 9 publications

References 36 publications

Hepatoprotective effect of silymarin

Hepatoprotective effect of silymarin

Silymarin-Loaded, Lactobionic Acid-Conjugated Porous PLGA Nanoparticles Induce Apoptosis in Liver Cancer Cells

Role of Silymarin in Cancer Treatment: Facts, Hypotheses, and Questions

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