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Updated: Jul 16, 2026

Isolation and Functional Analysis of Mitochondria from Cultured Cells and Mouse Tissue
09:27

Isolation and Functional Analysis of Mitochondria from Cultured Cells and Mouse Tissue

Published on: March 23, 2015

Lysosomal and mitochondrial pathways in miltefosine-induced apoptosis in U937 cells

Caroline Paris1, Jacques Bertoglio, Jacqueline Bréard

  • 1INSERM U749, Faculté de Pharmacie Paris-Sud. 5, rue Jean-Baptiste Clément 92290, Châtenay-Malabry, France.

Apoptosis : an International Journal on Programmed Cell Death
|March 10, 2007
PubMed

Insights

Hexadecylphosphocholine (HePC) triggers cancer cell death through both intrinsic mitochondrial and lysosomal pathways. Signaling crosstalk between these pathways and caspase activation are crucial for HePC-induced apoptosis.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Hexadecylphosphocholine (HePC) is an anticancer agent.
  • Its mechanism of action involves apoptosis induction, but signaling pathways are not fully understood.

Purpose of the Study:

  • To elucidate the signaling pathways involved in Hexadecylphosphocholine (HePC)-induced apoptosis.
  • To investigate the interplay between mitochondrial and lysosomal pathways in HePC-mediated cell death.

Main Methods:

  • Assessing caspase activation (caspase-9, -3, -8).
  • Monitoring cytochrome c release and Bax/Bid protein changes.
  • Evaluating lysosomal integrity, cathepsin B activity, and relocation.
  • Utilizing specific inhibitors (cathepsin B/L inhibitor, pancaspase inhibitor Q-VD-OPH) and Bcl-2 overexpression.

Main Results:

  • HePC activates caspases-9, -3, and -8 via the intrinsic pathway, involving cytochrome c release, Bax relocation, and Bid cleavage.
  • A lysosomal pathway with cathepsin B activation and cytosolic relocation contributes to HePC-induced apoptosis.
  • Evidence of signaling crosstalk between lysosomes and mitochondria.
  • Early lysosomal rupture is caspase-dependent, while Bcl-2 overexpression prevents lysosomal destabilization and cell death.

Conclusions:

  • HePC induces apoptosis through a complex interplay of intrinsic mitochondrial and lysosomal pathways.
  • Caspase activation and lysosomal integrity are critical components of HePC's anticancer effects.
  • Targeting these pathways could enhance HePC efficacy.

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