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TUCAN/CARDINAL/CARD8 and apoptosis resistance in non-small cell lung cancer cells

Agnieszka Checinska1, Giuseppe Giaccone, Bas S J Hoogeland

  • 1Department of Medical Oncology, VU University Medical Center, 1081 HV Amsterdam, The Netherlands. a.checinska@vumc.nl

BMC Cancer
|June 27, 2006
PubMed
Abstract

Insights

TUCAN does not inhibit caspase-9 activation or affect chemotherapy sensitivity in non-small cell lung cancer (NSCLC). This finding clarifies the mechanism behind drug resistance in NSCLC, suggesting TUCAN is not a viable therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Non-small cell lung cancer (NSCLC) exhibits resistance to chemotherapy, potentially due to inhibited caspase-9 activation.
  • Investigating the mechanism of caspase-9 inhibition is crucial for understanding and overcoming this clinical resistance.

Purpose of the Study:

  • To investigate the mechanism of caspase-9 inhibition in NSCLC cells.
  • To determine the role of TUCAN (a known caspase-9 inhibitor) in NSCLC chemosensitivity.

Main Methods:

  • Western blot and fluorogenic substrate assays (LEHD-AFC) to assess caspase-9 processing and activation.
  • Protein interaction assays, RNA interference, cell viability, and apoptosis assays to evaluate TUCAN's involvement.

Main Results:

  • Lung cancer cell lysates showed functional caspase-9 activation upon addition of cytochrome c and dATP, indicating an inhibitor's presence.
  • TUCAN, a reported caspase-9 inhibitor, was expressed in NSCLC cells, but direct interaction with procaspase-9 was not detected.
  • Down-regulating TUCAN via RNA interference did not restore cisplatin-induced caspase-9 activation or alter NSCLC sensitivity to cisplatin.

Conclusions:

  • Procaspase-9 is functional and activatable in lung cancer cell extracts with cytochrome c/dATP.
  • The inhibitory protein TUCAN does not play a role in inhibiting procaspase-9 or determining cisplatin sensitivity in NSCLC.

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