Cannabidiol induced apoptosis in human monocytes through mitochondrial permeability transition pore-mediated ROS

Hsin-Ying Wu1, Chung-Hsiung Huang2, Yi-Hsuan Lin3

  • 1Department and Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan; Laboratory Animal Center, National Health Research Institutes, Miaoli, Taiwan.

Insights

Cannabidiol (CBD) induces apoptosis in human monocytes by triggering mitochondrial damage and reactive oxygen species (ROS) production. This process involves the opening of the mitochondrial permeability transition pore (MPTP), leading to programmed cell death.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Cannabidiol (CBD) is known to induce apoptosis in immune cells.
  • Oxidative stress is a proposed mechanism for CBD-induced cell death.

Purpose of the Study:

  • To investigate the specific cellular mechanisms underlying CBD-induced apoptosis and oxidative stress in human monocytes.
  • To elucidate the role of mitochondria in CBD-mediated cell death.

Main Methods:

  • Human monocytes were exposed to varying concentrations and durations of CBD.
  • Assays were performed to measure reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP) depolarization, cardiolipin oxidation, and cytochrome c release.
  • Inhibitors such as cyclosporin A (CsA) and FK506 were used to probe mechanistic pathways.

Main Results:

  • CBD induced apoptosis in human monocytes in a time- and concentration-dependent manner.
  • CBD exposure led to rapid mitochondrial membrane potential depolarization and cardiolipin oxidation, followed by ROS generation and cytochrome c release.
  • CBD-induced apoptosis and mitochondrial dysfunction were significantly inhibited by CsA, implicating the mitochondrial permeability transition pore (MPTP) in the process.

Conclusions:

  • CBD induces apoptosis in human monocytes primarily through the opening of the MPTP.
  • Mitochondrial dysfunction, including ROS generation and MMP depolarization, is a key event in CBD-induced monocyte apoptosis.
  • These findings provide critical insights into the molecular mechanisms of CBD's effects on immune cells.

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