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CK2 inhibition induces apoptosis via the ER stress response

Andrea Hessenauer1, Carolin C Schneider, Claudia Götz

  • 1Allgemeine Zoologie und Endokrinologie, Universität Ulm, Ulm, Germany. andrea.hessenauer@uni-ulm.de

Cellular Signalling
|September 3, 2010
PubMed

Insights

Protein kinase CK2 inhibition induces apoptosis in prostate cancer cells. The CK2 inhibitor TBB activates endoplasmic reticulum stress, upregulating DR5 and leading to programmed cell death in LNCaP cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Protein kinase CK2 (CK2) is highly expressed in tumor cells, promoting survival by inhibiting apoptosis.
  • CK2 is a validated cancer target, as its inhibition can induce programmed cell death.
  • The CK2 inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB) has shown potential in cancer therapy.

Purpose of the Study:

  • To investigate the induction of apoptosis by the CK2 inhibitor TBB in prostate tumor cells.
  • To elucidate the molecular mechanisms underlying TBB-induced apoptosis in different prostate cancer cell lines (LNCaP and PC-3).

Main Methods:

  • Treatment of LNCaP and PC-3 prostate cancer cells with the CK2 inhibitor TBB.
  • Analysis of apoptosis induction, mitochondrial pathway activation (bcl-2 downregulation, cytochrome c release), and endoplasmic reticulum (ER) stress response.
  • Assessment of caspase 9 activation and death receptor (DR5) expression.

Main Results:

  • LNCaP cells, but not PC-3 cells, responded to CK2 inhibition with apoptosis.
  • Both cell lines exhibited mitochondrial pathway activation, evidenced by bcl-2 downregulation and cytochrome c release.
  • Caspase 9 activation was not detected; however, TBB induced an ER stress response in LNCaP cells, leading to DR5 upregulation and subsequent apoptosis.

Conclusions:

  • CK2 inhibition by TBB induces apoptosis in prostate cancer cells through both mitochondrial and ER stress-dependent pathways.
  • The ER stress response and subsequent DR5 upregulation play a critical role in TBB-induced apoptosis in LNCaP cells.
  • CK2 represents a significant therapeutic target for prostate cancer, with TBB demonstrating potential for inducing tumor cell death.

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