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Estradiol induces JNK-dependent apoptosis in glioblastoma cells

Nedret Altiok1, Melike Ersoz, Meral Koyuturk

  • 1Department of Pharmacology, Yeni Yuzyil University School of Medicine, Istanbul, Turkey.

Oncology Letters
|August 1, 2012
PubMed

Insights

High concentrations of 17-β-estradiol (estradiol) inhibit glioblastoma cell growth and induce apoptosis via the c-jun NH(2)-terminal kinase (JNK) pathway. This suggests potential for JNK-based therapies to sensitize tumors to chemotherapy.

Area of Science:

  • Neuroscience
  • Oncology
  • Endocrinology

Background:

  • Estrogens regulate cellular functions in various tissues, including the brain.
  • Glioblastoma is a complex brain tumor with significant unmet therapeutic needs.

Purpose of the Study:

  • To investigate the concentration-dependent signaling mechanisms of 17-β-estradiol (estradiol) in glioblastoma cells.
  • To elucidate the role of the c-jun NH(2)-terminal kinase (JNK) pathway in estradiol's effects on glioblastoma.

Main Methods:

  • Cell viability assessed using trypan blue exclusion assay.
  • Cell growth and kinase activities evaluated via immunocytochemistry and Western blotting.
  • JNK signaling pathway blockade to determine its involvement.

Main Results:

  • High estradiol concentrations inhibited growth and induced apoptosis in C6 rat glioma and T98G human glioblastoma cells.
  • Blocking the JNK signaling pathway abrogated estradiol's inhibitory and apoptotic effects.
  • The JNK/c-jun signaling cascade is critical for high-dose estradiol's impact on glioblastoma cells.

Conclusions:

  • High concentrations of estradiol exert anti-cancer effects on glioblastoma cells through the JNK/c-jun pathway.
  • These findings suggest potential therapeutic strategies involving JNK modulation to enhance chemotherapy efficacy in estrogen-sensitive tumors.

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