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 72 h. 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 COD 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 COD between precultured and freshly isolated monocytes, which was closely associated with the cellular level of glutathione and the antioxidative capability of the cells. (C) 2010 Elsevier Inc All rights reserved