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Curcumin induces apoptosis in p53-null Hep3B cells through a TAp73/DNp73-dependent pathway

Jinhong Wang1, Hai Xie2, Feng Gao3

  • 1Department of Pharmacology, Weifang Medical University, Weifang, 261053, China. jinrongwangwf@126.com.

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
|October 23, 2015
PubMed

Insights

Curcumin induces apoptosis in cancer cells by activating p73-dependent pathways. This involves DNA damage, altered p73 ratios, and mitochondrial dysfunction, leading to programmed cell death.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Biochemistry

Background:

  • Curcumin exhibits anticancer properties, potentially via p53-dependent apoptosis.
  • The p73 gene, part of the p53 family, encodes tumor suppressor (TAp73) and oncogenic (DNp73) isoforms.
  • Understanding p73's role in curcumin-induced apoptosis is crucial for cancer therapy.

Purpose of the Study:

  • To elucidate the p73-dependent mechanisms underlying curcumin-induced apoptosis.
  • To investigate curcumin's effects in a p53-deficient cellular model overexpressing p73 isoforms.

Main Methods:

  • Established p53-deficient Hep3B cells overexpressing TAp73 and DNp73 (Hep3B(TAp73/DNp73)).
  • Treated cells with curcumin (40 and 80 μM).
  • Assessed DNA damage, TAp73/DNp73 ratio, apoptosis, mitochondrial membrane potential, cytochrome c release, and caspase/PARP cleavage.

Main Results:

  • Curcumin induced DNA damage and apoptosis in Hep3B(TAp73/DNp73) cells.
  • A significant increase in the TAp73/DNp73 ratio was observed post-curcumin treatment.
  • Apoptosis correlated with mitochondrial pathway activation, including cytochrome c release and caspase cascade activation.

Conclusions:

  • Curcumin triggers apoptosis through a p73-dependent mechanism.
  • The mitochondria-mediated pathway is integral to curcumin's apoptotic effect via p73.
  • This study highlights p73's critical role in mediating curcumin's anticancer activity.
Keywords:
ApoptosisCurcuminDNA damageDNp73TAp73

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