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Endoplasmic reticulum stress associated with caspases-4 and -2 mediates korbazol-induced B-chronic lymphocytic

S Popovic1, D Baskic, P Djurdjevic

  • 1Department of Microbiology and Immunology, Faculty of Medicine, University of Kragujevac, Kragujevac, Serbia. suza_popovic@yahoo.com

Journal of B.U.ON. : Official Journal of the Balkan Union of Oncology
|January 14, 2011
PubMed
Abstract

Insights

Korbazol induces cell death in B-cell chronic lymphocytic leukemia (B-CLL) by activating caspases-2 and -4 and mobilizing calcium, suggesting endoplasmic reticulum stress is involved in this natural product

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • B-cell chronic lymphocytic leukemia (B-CLL) is an incurable hematologic malignancy.
  • Drug resistance is a significant challenge in B-CLL treatment.
  • Natural products offer potential therapeutic avenues for B-CLL.

Purpose of the Study:

  • To elucidate the mechanism of apoptosis induced by the natural product Korbazol in B-CLL cells.
  • To identify key molecular players involved in Korbazol-mediated cell death.

Main Methods:

  • Peripheral blood mononuclear cells from B-CLL patients were treated with Korbazol.
  • Caspase inhibitors (caspase-2, -3, -4, -8, -9) and a calcium chelator (BAPTA-AM) were used.
  • Cytochrome C release was assessed to evaluate mitochondrial pathway involvement.

Main Results:

  • Korbazol-induced cell death was reduced by inhibitors of caspase-2 and -4, but not caspase-8 or -9.
  • No significant cytochrome C release was observed, indicating the mitochondrial pathway was not primarily involved.
  • Intracellular calcium chelation with BAPTA-AM nearly abolished the cytotoxic effect of Korbazol.

Conclusions:

  • Korbazol-induced apoptosis in B-CLL cells involves the activation of caspases-2 and -4.
  • Mobilization of intracellular calcium is crucial for Korbazol's cytotoxic effect.
  • These findings suggest that endoplasmic reticulum (ER) stress plays a role in Korbazol-mediated apoptosis.

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