The Mechanism of Cannabidiol-Mediated Apoptosis in Human Monocytes
Date Issued
2010
Date
2010
Author(s)
Chang, An-Chi
Abstract
Cannabidiol (CBD), the major non-psychoactive cannabinoid, has been documented to induce apoptosis in a variety of immune cells, including primary lymphocytes and transformed lymphocytic and monocytic cell lines. In contrast, human peripheral blood monocytes precultured for 72 h have been reported to be insensitive to CBD-mediated apoptosis. The objective of this study was to investigate the pro-apoptotic effect of CBD on monocytes that were either freshly isolated or precultured for 72 h. The results showed that CBD markedly enhanced apoptosis of freshly isolated monocytes in a concentration-dependent manner, whereas 72 h-precultured monocytes were insensitive. Exposure of monocytes to CBD elicited an early production of reactive oxygen species (ROS), including superoxide anion, hydrogen peroxide and hydroxyl radicals. Pretreatment of monocytes with antioxidants, including N-acetyl-L-cysteine, catalase, sodium pyruvate, dimethylthiourea and 4,5-dihydroxy-1,3-benzenedisulfonic acid, significantly attenuated the apoptosis induced by CBD. In addition, precultured monocytes contained a greater level of glutathione (GSH), superoxide dismutase (SOD) and heme oxygenase-1 (HO-1), as compared to the freshly isolated cells. CBD diminished the level of cellular GSH and SOD in fresh monocytes. Zinc protoporphyrin, a specific HO-1 inhibitor, restored the sensitiveness of precultured monocytes to CBD-mediated apoptosis. The antioxidant ability of monocytes may influence the apoptotic effect of CBD. The mechanism of CBD induced oxidative stress is unclear. The vanilloid receptor type 1 (VR1) antagonist capsazepine attenuated CBD induced apoptosis, suggesting that VR1 may be a potential target involved in CBD-mediated monocytes apoptosis. In summary, the present study demonstrated a contrasting pro-apoptotic effect of CBD between precultured and freshly isolated monocytes, which was closely associated with the antioxidative capability of the cells.
Subjects
cannabidiol
reactive oxygen species
glutathione
superoxide dismutase
heme oxygenase-1
Type
thesis
File(s)![Thumbnail Image]()
Loading...
Name
ntu-99-R97629009-1.pdf
Size
23.32 KB
Format
Adobe PDF
Checksum
(MD5):3059d7decec66e17bc5664d36e53ce65