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Dentatin from Clausena excavata Induces Apoptosis in HepG2 Cells via Mitochondrial Mediated Signaling

A Reenaa Joys Andas1, Ahmad Bustamam Abdul, Heshu Sulaiman Rahman

  • 1UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Malaysia

Asian Pacific Journal of Cancer Prevention : APJCP
|June 2, 2015
PubMed

Insights

Dentatin (DTN) shows promise as a natural compound to combat hepatocellular carcinoma (HCC). This study found DTN effectively inhibits liver cancer cell growth and induces apoptosis, offering a potential new therapeutic avenue.

Area of Science:

  • Pharmacology
  • Molecular Biology
  • Hepatology

Background:

  • Hepatocellular carcinoma (HCC) presents significant global health challenges due to high incidence and mortality.
  • Existing treatments for HCC are limited and often associated with adverse side effects.

Purpose of the Study:

  • To evaluate the antiproliferative effects of dentatin (DTN) on hepatocellular carcinoma (HCC) cells.
  • To investigate the preliminary molecular mechanisms underlying DTN's induction of apoptosis in HCC.

Main Methods:

  • In vitro antiproliferative assays on HepG2 (HCC) and WRL-68 (normal liver) cells.
  • Cell cycle analysis to determine cell cycle arrest.
  • Caspase assays to measure apoptosis-related enzyme activity.
  • Western blotting to analyze key proteins in apoptotic signaling pathways (NF-κB, Bcl-2 family, cytochrome c).

Main Results:

  • Dentatin (DTN) significantly inhibited HepG2 cell proliferation (IC50 = 12.0 μg/mL) without toxicity to normal liver cells (IC50 > 50 μg/mL).
  • DTN induced G0/G1 cell cycle arrest and apoptosis, evidenced by increased caspase-3 and caspase-9 activity.
  • DTN suppressed NF-κB signaling, leading to mitochondrial pathway activation (upregulation of cytochrome c and Bax, downregulation of Bcl-2 and Bcl-xL).

Conclusions:

  • Dentatin (DTN) demonstrates potent anticancer activity against hepatocellular carcinoma (HCC) cells in vitro.
  • DTN induces apoptosis through the mitochondrial pathway, involving caspase activation and modulation of Bcl-2 family proteins.
  • DTN is a promising natural compound candidate for further development as a targeted therapy for HCC.

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