Cytotoxic effects of suramin against HepG2 cells through activation of intrinsic apoptotic pathway

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

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Purpose: To investigate the cytotoxic activity of suramin against HepG2 human HCC cell line. Methods: HepG2 cells were treated with 15, 30 and 45 uM suramin. HepG2 cell proliferation was measured by MTT and lactate dehydrogenase (LDH) assays. Heparan sulfate proteoglycans (HSPGs), glucuronic acid and glucosamine levels were measured. Moreover, apoptosis was assessed by measuring caspase-8 and caspase-9 activities. The effect of suramin on HepG2 cells was compared with the same doses of a standard drug, cisplatin. Results: Suramin blocked heparanase leading to dose-dependent increase in HSPGs and reduction in glucuronic acid and glucosamine levels. Suramin reduced HepG2 cells survival and showed cell cytotoxicity in a dose-dependent manner with LD50 45.04 uM, compared with cisplatin (LD50 28.9 uM) (p<0.05). Moreover, suramin was able to increase the activity of caspase-9 but not of caspase-8. Conclusion: Suramin possesses cytotoxic properties, which can be partially explained by its ability to inhibit heparanase and restore HSPGs. Suramin activates intrinsic apoptosis without affecting the extrinsic pathway.

Original languageEnglish (US)
Pages (from-to)1048-1054
Number of pages7
JournalJournal of B.U.ON.
Volume19
Issue number4
StatePublished - Oct 1 2014
Externally publishedYes

Keywords

  • Caspase-8
  • Caspase-9
  • Glucosamine
  • Glucuronic acid
  • Heparan sulfate proteoglycans
  • Heparanase

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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  • Cite this

    Tayel, A., Ebrahim, M. A., Ibrahim, A. S., El-Gayar, A. M., & Al-Gayyar, M. M. (2014). Cytotoxic effects of suramin against HepG2 cells through activation of intrinsic apoptotic pathway. Journal of B.U.ON., 19(4), 1048-1054.