Eurycomanone induce apoptosis in HepG2 cells via up-regulation of p53

Yusmazura Zakaria1, Asmah Rahmat, Azimahtol Hawariah Lope Pihie

  • 1Institute of Biosciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia. iema1210@gmail.com

Abstract

Insights

Eurycomanone, a compound from Eurycoma longifolia Jack, effectively kills liver cancer cells (HepG2) by triggering apoptosis. This process involves regulating key proteins like p53 and Bax, showing its potential as an anti-cancer agent.

Area of Science:

  • Pharmacology
  • Molecular Biology
  • Biochemistry

Background:

  • Eurycomanone, a natural compound from Eurycoma longifolia Jack, exhibits known cytotoxic effects against various cancer cell lines.
  • Previous research indicated the cytotoxic potential of eurycomanone, necessitating further investigation into its specific mechanisms.

Purpose of the Study:

  • To investigate the in vitro cytotoxicity of eurycomanone against human hepatocellular carcinoma (HepG2) cells.
  • To elucidate the mode of action underlying eurycomanone-induced cell death in HepG2 cells.

Main Methods:

  • Cytotoxicity was assessed using the MTT assay.
  • Apoptosis was detected via Hoechst 33258 nuclear staining and Annexin-V/propidium iodide flow cytometry.
  • Protein expression levels of Bax, Bcl-2, p53, and cytochrome C were analyzed by flow cytometry.

Main Results:

  • Eurycomanone demonstrated significant cytotoxicity against HepG2 cells, with minimal toxicity observed in normal liver cells (Chang's liver and WLR-68).
  • Apoptosis was confirmed as the primary mode of cell death, evidenced by chromatin condensation, DNA fragmentation, and apoptotic body formation.
  • Eurycomanone treatment led to the up-regulation of p53 tumor suppressor protein and the pro-apoptotic Bax protein, alongside a down-regulation of the anti-apoptotic Bcl-2 protein.
  • Increased cytochrome C levels in the cytosol further supported the induction of apoptosis.

Conclusions:

  • Eurycomanone exhibits potent cytotoxicity against HepG2 liver cancer cells.
  • The mechanism involves the induction of apoptosis, mediated by the up-regulation of p53 and Bax, and the down-regulation of Bcl-2.
  • These findings highlight eurycomanone's potential as a therapeutic agent for hepatocellular carcinoma.

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