Cannabidiol induced a contrasting pro-apoptotic effect between freshly isolated and precultured human monocytes.
It has been documented that cannabidiol (CBD) induced apoptosis in a variety of transformed cells, including lymphocytic and monocytic leukemias. In contrast, a differential sensitivity between normal lymphocytes and monocytes to CBD-mediated apoptosis has been reported. The present study investigated the pro-apoptotic effect of CBD on human peripheral monocytes that were either freshly isolated or precultured for 72h. CBD markedly enhanced apoptosis of freshly isolated monocytes in a time- and concentration-dependent manner, whereas precultured monocytes were insensitive. By comparison, both cells were sensitive to doxorubicin-induced apoptosis. CBD significantly diminished the cellular thiols and glutathione in freshly isolated monocytes. The apoptosis induced by CBD was abrogated in the presence of N-acetyl-L-cysteine, a precursor of glutathione. In addition, precultured monocytes contained a significantly greater level of glutathione and heme oxygenase-1 (HO-1) compared to the freshly isolated cells. The HO-1 competitive inhibitor zinc protoporphyrin partially but significantly restored the sensitivity of precultured monocytes to CBD-mediated apoptosis. Collectively, our results demonstrated a contrasting pro-apoptotic effect of CBD between precultured and freshly isolated monocytes, which was closely associated with the cellular level of glutathione and the antioxidative capability of the cells.
Wu
Hsin-Ying
HY
Department and Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan.
Chang
An-Chi
AC
Department and Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan.
Wang
Chia-Chi
CC
Department and Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan.
Kuo
Fu-Hua
FH
Department and Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan.
Lee
Chi-Ya
CY
Department and Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan.
Liu
Der-Zen
DZ
Graduate Institute of Biomedical Materials and Engineering, Taipei Medical University, Taipei, Taiwan.
Jan
Tong-Rong
TR
Department and Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan.
D000111:Acetylcysteine / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002185:Cannabidiol / Q000494:pharmacology*; D002478:Cells, Cultured; D004317:Doxorubicin / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000378:metabolism
D000975:Antioxidants; D011524:Protoporphyrins; D013438:Sulfhydryl Compounds; C017803:zinc protoporphyrin; D002185:Cannabidiol; D004317:Doxorubicin; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D005978:Glutathione; D000111:Acetylcysteine