Abstract
Apoptosis, a well-known pattern of programmed cell death, occurs in multicellular organisms not only for controlling tissue homeostasis but also for getting rid of severely damaged cells in order to protect the redundant growth of abnormal cells undergoing cancerous cells. The epidermis of the human skin, composed largely of keratinocytes (KCs), is renewed continuously. Therefore, KCs apoptosis plays a critical role in the maintenance of epidermis structure and function. However, regulated cell death can be disturbed by environmental factors especially ultraviolet radiation (UV) B, leading to the formation of sunburn cells (KCs undergoing UVB-induced apoptosis) and impairing the skin integrity. In the present study, we firstly reported the potential of the natural artocarpin (NAR) to regulate UVB-induced human KCs apoptosis. The NAR showed antilipid peroxidation with an IC50 value of 18.2 ± 1.6 μg/mL, according to TBARS assay while the IC50 value of trolox, a well-known antioxidant, was 7.3 ± 0.8 μg/mL. For cell-based studies, KCs were pretreated with 3.1 μg/mL of the NAR for 24 hr and then exposed to UVB at 55 mJ/cm2. Our data indicated that the NAR pretreatment reduces UVB-induced oxidative stress by scavenging free radicals and nitric oxide and therefore prevents reactive oxygen species (ROS) and reactive nitrogen species- (RNS-) mediated apoptosis. The NAR pretreatment has been shown also to reduce the UVB-induced cyclobutane pyrimidine dimer (CPD) lesions by absorbing UVB radiation and regulating the cell cycle phase. Additionally, the NAR pretreatment was found to modulate the expression of cleaved caspases-3 and 8 that trigger different signalling cascades leading to apoptosis. Thus, these results provide a basis for the investigation of the photoprotective effect of the NAR isolated from A. altilis heartwood and suggest that it can be potentially used as an agent against UVB-induced skin damages.