Suramin inhibits hepatic tissue damage in hepatocellular carcinoma through deactivation of heparanase enzyme

Ahmed Tayel, Khaled H. Abd El Galil, Mohamed A. Ebrahim, Ahmed Salah Ibrahim, Amal M. El-Gayar, Mohammed M.H. Al-Gayyar

Research output: Contribution to journalArticle

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Abstract

Hepatocellular carcinoma (HCC) is resistant to conventional chemotherapy, and is rarely amenable to radiotherapy. Heparanase, enzyme attacks heparan sulfate proteoglycans (HSPGs), is preferentially expressed in human tumors and its overexpression in low-metastatic tumor confers a highly invasive phenotype in experimental animals. Meanwhile, high doses of suramin dramatically increase tissue glycosaminoglycans due, in part, to inhibition of heparanase enzymes. Therefore, the following study was conducted to evaluate the chemopreventive and hepatoprotective effects of suramin in in-vivo model of HCC. Therefore, HCC was induced in SD rats by thioacetamide (200 mg/kg) in presence/absence of suramin (20 mg/kg). Liver impairment was assessed by measuring serum α-fetoprotein and investigating liver sections stained with Hematoxylin/Eosin. Hepatic HSPGs and heparanse were measured by ELISA. Glucosamine and glucuronic acid were measured by chemical methods. Gene expression of fibroblast growth factor (FGF)-2 and caspase-3 was measured. Apoptotic pathway was evaluated by measuring the activity of caspase-3/8/9. Suramin increased the animal survival and decreased serum α-fetoprotein. In addition, suramin ameliorated fibrosis and massive hepatic tissue breakdown. Suramin restored hepatic HSPGs and reduced the activity of hepatic heparanase leading to decreased hepatic levels of glucosamine and glucuronic acid. Moreover, suramin reduced the gene expression of FGF-2 and caspase-3. Finally, suramin blocked the elevated activity of caspase-3/8/9. In conclusion, surmain showed antitumor activity as well as hepatoprotective effects. Besides its antioxidant activity, other mechanisms are involved including restoration of HSPGs and inhibition of heparanase and FGF-2. Suramin inhibits intrinsic and extrinsic apoptotic pathway. Targeting HSPGs expression is potential therapeutic target for HCC.

Original languageEnglish (US)
Pages (from-to)151-160
Number of pages10
JournalEuropean Journal of Pharmacology
Volume728
Issue number1
DOIs
StatePublished - Apr 5 2014
Externally publishedYes

Fingerprint

Suramin
Hepatocellular Carcinoma
Heparan Sulfate Proteoglycans
Liver
Enzymes
Caspase 3
Fibroblast Growth Factor 2
Fetal Proteins
Glucuronic Acid
Caspase 8
Glucosamine
Thioacetamide
Gene Expression
heparanase
Hematoxylin
Eosine Yellowish-(YS)
Glycosaminoglycans
Serum
Neoplasms
Fibrosis

Keywords

  • Extrinsic cell death
  • Fibroblast Growth Factor (FGF)-2
  • Glucosamine
  • Glucuronic acid
  • Heparan sulfate proteoglycans (HSPGs)
  • Intrinsic cell death

ASJC Scopus subject areas

  • Pharmacology

Cite this

Tayel, A., Abd El Galil, K. H., Ebrahim, M. A., Ibrahim, A. S., El-Gayar, A. M., & Al-Gayyar, M. M. H. (2014). Suramin inhibits hepatic tissue damage in hepatocellular carcinoma through deactivation of heparanase enzyme. European Journal of Pharmacology, 728(1), 151-160. https://doi.org/10.1016/j.ejphar.2014.02.001

Suramin inhibits hepatic tissue damage in hepatocellular carcinoma through deactivation of heparanase enzyme. / Tayel, Ahmed; Abd El Galil, Khaled H.; Ebrahim, Mohamed A.; Ibrahim, Ahmed Salah; El-Gayar, Amal M.; Al-Gayyar, Mohammed M.H.

In: European Journal of Pharmacology, Vol. 728, No. 1, 05.04.2014, p. 151-160.

Research output: Contribution to journalArticle

Tayel, A, Abd El Galil, KH, Ebrahim, MA, Ibrahim, AS, El-Gayar, AM & Al-Gayyar, MMH 2014, 'Suramin inhibits hepatic tissue damage in hepatocellular carcinoma through deactivation of heparanase enzyme', European Journal of Pharmacology, vol. 728, no. 1, pp. 151-160. https://doi.org/10.1016/j.ejphar.2014.02.001
Tayel, Ahmed ; Abd El Galil, Khaled H. ; Ebrahim, Mohamed A. ; Ibrahim, Ahmed Salah ; El-Gayar, Amal M. ; Al-Gayyar, Mohammed M.H. / Suramin inhibits hepatic tissue damage in hepatocellular carcinoma through deactivation of heparanase enzyme. In: European Journal of Pharmacology. 2014 ; Vol. 728, No. 1. pp. 151-160.
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AU - El-Gayar, Amal M.

AU - Al-Gayyar, Mohammed M.H.

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AB - Hepatocellular carcinoma (HCC) is resistant to conventional chemotherapy, and is rarely amenable to radiotherapy. Heparanase, enzyme attacks heparan sulfate proteoglycans (HSPGs), is preferentially expressed in human tumors and its overexpression in low-metastatic tumor confers a highly invasive phenotype in experimental animals. Meanwhile, high doses of suramin dramatically increase tissue glycosaminoglycans due, in part, to inhibition of heparanase enzymes. Therefore, the following study was conducted to evaluate the chemopreventive and hepatoprotective effects of suramin in in-vivo model of HCC. Therefore, HCC was induced in SD rats by thioacetamide (200 mg/kg) in presence/absence of suramin (20 mg/kg). Liver impairment was assessed by measuring serum α-fetoprotein and investigating liver sections stained with Hematoxylin/Eosin. Hepatic HSPGs and heparanse were measured by ELISA. Glucosamine and glucuronic acid were measured by chemical methods. Gene expression of fibroblast growth factor (FGF)-2 and caspase-3 was measured. Apoptotic pathway was evaluated by measuring the activity of caspase-3/8/9. Suramin increased the animal survival and decreased serum α-fetoprotein. In addition, suramin ameliorated fibrosis and massive hepatic tissue breakdown. Suramin restored hepatic HSPGs and reduced the activity of hepatic heparanase leading to decreased hepatic levels of glucosamine and glucuronic acid. Moreover, suramin reduced the gene expression of FGF-2 and caspase-3. Finally, suramin blocked the elevated activity of caspase-3/8/9. In conclusion, surmain showed antitumor activity as well as hepatoprotective effects. Besides its antioxidant activity, other mechanisms are involved including restoration of HSPGs and inhibition of heparanase and FGF-2. Suramin inhibits intrinsic and extrinsic apoptotic pathway. Targeting HSPGs expression is potential therapeutic target for HCC.

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