Disease-Dependent Antiapoptotic Effects of Cannabidiol for Keratinocytes Observed upon UV Irradiation

Abstract

Although apoptosis of keratinocytes has been relatively well studied, there is a lack of information comparing potentially proapoptotic treatments for healthy and diseased skin cells. Psoriasis is a chronic autoimmune-mediated skin disease manifested by patches of hyperproliferative keratinocytes that do not undergo apoptosis. UVB phototherapy is commonly used to treat psoriasis, although this has undesirable side effects, and is often combined with anti-inflammatory compounds. The aim of this study was to analyze if cannabidiol (CBD), a phytocannabinoid that has anti-inflammatory and antioxidant properties, may modify the proapoptotic effects of UVB irradiation in vitro by influencing apoptotic signaling pathways in donor psoriatic and healthy human keratinocytes obtained from the skin of five volunteers in each group. While CBD alone did not have any major effects on keratinocytes, the UVB treatment activated the extrinsic apoptotic pathway, with enhanced caspase 8 expression in both healthy and psoriatic keratinocytes. However, endoplasmic reticulum (ER) stress, characterized by increased expression of caspase 2, was observed in psoriatic cells after UVB irradiation. Furthermore, decreased p-AKT expression combined with increased 15-d-PGJ2 level and p-p38 expression was observed in psoriatic keratinocytes, which may promote both apoptosis and necrosis. Application of CBD partially attenuated these effects of UVB irradiation both in healthy and psoriatic keratinocytes, reducing the levels of 15-d-PGJ2, p-p38 and caspase 8 while increasing Bcl2 expression. However, CBD increased p-AKT only in UVB-treated healthy cells. Therefore, the reduction of apoptotic signaling pathways by CBD, observed mainly in healthy keratinocytes, suggests the need for further research into the possible beneficial effects of CBD.

Influence of Inhibition of COX-2-Dependent Lipid Metabolism on Regulation of UVB-Induced Keratinocytes Apoptosis by Cannabinoids

“…CBD does not change the percentage of cells undergoing apoptosis, even though it decreases the expression of caspases 3, 8, and 9 in the case of keratinocytes otherwise untreated. These results confirm the previously observed protective properties of cannabidiol [ 56 ]. However, a stronger inhibition of caspase expression is observed in the case of celecoxib-treated cells in which cannabidiol also decreases the number of cells undergoing apoptosis.…”

The molecular activity of cannabidiol in the regulation of Nrf2 system interacting with NF-κB pathway under oxidative stress

“…However, the study in Wistar rats indicated CBD (5 mg/kg)-induced PI3K/AKT and MAPK/ERK pathways associated with reducing reperfusion myocardial damage [ 86 ]. Moreover, CBD (4 μM) has been shown to reduce the p38 level in keratinocytes in the skin of healthy and psoriatic people [ 87 ]. It may therefore be suggested that changes in CBD-mediated AKT, as well as MAPK signaling, may play an important role in determining the cellular response to regulate intracellular homeostasis in pathological conditions by modulating Nrf2 transcription.…”

Photoprotective Effects of Cannabidiol against Ultraviolet-B-Induced DNA Damage and Autophagy in Human Keratinocyte Cells and Mouse Skin Tissue

“…For instance, in vitro studies using 2D- and 3D-cultured skin cell models showed that CBD protects human skin keratinocyte cells from UV irradiation by alleviating cellular oxidative stress [ 2 ]. In addition, CBD reduces ultraviolet B (UVB)-induced apoptotic pathways by modulating cell death-related proteins such as pro-apoptotic prostaglandin, p-p38, and caspase-8 [ 3 ]. CBD has also been reported to restore redox balance by mediating UVB-induced lipid peroxidation products [ 4 ].…”