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Updated: Feb 8, 2026

Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess
Published on: June 1, 2022
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.
Abstract:
Cannabidiol (CBD) has been reported to induce apoptosis in immune cells through oxidative stress-related mechanisms. The objective of the present study was to investigate the cellular mechanisms for CBD-induced apoptosis and oxidative stress in human monocytes. Exposure of freshly isolated human monocytes to CBD induced apoptosis in a time- and concentration-dependent manner. Time-course analyses revealed the induction of intracellular reactive oxygen species (ROS) at 1-2 h post CBD (16 μM) exposure. By comparison, the CBD treatment rapidly elicited the depolarization of mitochondrial membrane potential (MMP) within 5 min, and the oxidation of cardiolipin, a major lipid component of the mitochondrial inner membrane, within 15 min. Moreover, CBD induced the release of cytochrome c (Cyt c) from mitochondria. Mechanistic studies revealed that CBD-induced ROS production and apoptosis were not associated with the alteration of mitochondrial superoxide dismutase activity, the electron leakage through mitochondrial respiratory chain, and Fe2+- and Ca2+-mediated mechanisms. In contrast, CBD-induced apoptosis and MMP depolarization were markedly attenuated by the mitochondrial permeability transition pore (MPTP) inhibitor cyclosporin A (CsA), but not the calcineurin inhibitor FK506. Furthermore, CsA prevented cardiolipin oxidation and the MPTP opening induced by CBD. The present study suggests that CBD acts on the mitochondria to elicit ROS generation and apoptosis through MPTP opening and provides critical insights into the cellular mechanisms for CBD-induced oxidative stress in apoptotic monocytes.
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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