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Selenium activates p53 and p38 pathways and induces caspase-independent cell death in cervical cancer cells

E Rudolf1, K Rudolf, M Cervinka

  • 1Department of Medical Biology and Genetics, Charles University in Prague, Faculty of Medicine in Hradec Králové, Hradec Králové, Czech Republic. rudolf@lfhk.cuni.cz

Cell Biology and Toxicology
|July 5, 2007
PubMed

Insights

Sodium selenite triggers programmed cell death in cervical cancer cells by inducing oxidative stress and activating p53 and p38 pathways. This leads to caspase-independent apoptosis, primarily through mitochondrial dysfunction.

Area of Science:

  • Oncology
  • Cell Biology
  • Toxicology

Background:

  • Cervical carcinoma is a significant global health concern.
  • Understanding the molecular mechanisms of chemotherapy-induced cell death is crucial for developing effective treatments.

Purpose of the Study:

  • To elucidate the mechanisms of sodium selenite-induced cell death in cervical carcinoma cells.
  • To investigate the roles of oxidative stress, p53, p38, and mitochondrial pathways in selenite toxicity.

Main Methods:

  • HeLa Hep-2 cells were exposed to sodium selenite (5 and 50 micromol/L) for 24 hours.
  • Assessed DNA synthesis suppression, DNA damage (histone H2A.X phosphorylation), and oxidative stress markers.
  • Investigated p53 and p38 pathway activation, Bax protein levels, and mitochondrial dynamics (AIF and Smac/Diablo release).
  • Utilized specific inhibitors (MnTMPyP, buthionine sulfoximine, SB 203580, Pifithrin-alpha) and caspase activity assays.

Main Results:

  • Sodium selenite caused dose- and time-dependent DNA synthesis suppression and DNA damage.
  • Oxidative stress, indicated by MnTMPyP and buthionine sulfoximine effects, played a significant role.
  • Selenite activated p53 and p38 pathways, leading to Bax accumulation and mitochondrial release of AIF and Smac/Diablo.
  • Cell death was confirmed as caspase-independent apoptosis.

Conclusions:

  • Sodium selenite induces caspase-independent apoptosis in cervical carcinoma cells.
  • The primary mechanism involves oxidative stress-mediated activation of p53 and p38 signaling pathways.
  • Mitochondrial dynamics and subsequent AIF/Smac/Diablo release are critical in selenite-induced cell death.

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