Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok 65000, Thailand.
Department of Biochemistry, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand.
Oxid Med Cell Longev. 2020 Sep 19;2020:1042451. doi: 10.1155/2020/1042451. eCollection 2020.
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 IC value of 18.2 ± 1.6 g/mL, according to TBARS assay while the IC value of trolox, a well-known antioxidant, was 7.3 ± 0.8 g/mL. For cell-based studies, KCs were pretreated with 3.1 g/mL of the NAR for 24 hr and then exposed to UVB at 55 mJ/cm. 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 heartwood and suggest that it can be potentially used as an agent against UVB-induced skin damages.
细胞凋亡是一种已知的细胞程序性死亡模式,不仅在多细胞生物中控制组织内稳态,而且还清除严重受损的细胞,以保护发生癌变的异常细胞的过度生长。人体皮肤的表皮主要由角质形成细胞(KCs)组成,它会不断更新。因此,KCs 凋亡在维持表皮结构和功能方面起着关键作用。然而,受环境因素特别是紫外线 B(UVB)的影响,细胞的程序性死亡可能会受到干扰,导致晒伤细胞(KCs 经历 UVB 诱导的凋亡)的形成,并损害皮肤完整性。在本研究中,我们首次报道了天然阿魏酸(NAR)调节 UVB 诱导的人 KCs 凋亡的潜力。根据 TBARS 测定,NAR 具有抗脂质过氧化作用,IC 值为 18.2±1.6μg/mL,而众所周知的抗氧化剂 trolox 的 IC 值为 7.3±0.8μg/mL。在细胞水平研究中,将 KCs 用 3.1μg/mL 的 NAR 预处理 24 小时,然后用 55mJ/cm 的 UVB 照射。我们的数据表明,NAR 预处理通过清除自由基和一氧化氮来减少 UVB 诱导的氧化应激,从而防止活性氧(ROS)和活性氮(RNS)介导的细胞凋亡。NAR 预处理还通过吸收 UVB 辐射和调节细胞周期相来减少 UVB 诱导的环丁烷嘧啶二聚体(CPD)损伤。此外,发现 NAR 预处理可调节引发不同信号级联反应导致细胞凋亡的裂解半胱天冬酶-3 和 8 的表达。因此,这些结果为研究从心材中分离出的 NAR 的光保护作用提供了依据,并表明它可潜在用作对抗 UVB 诱导的皮肤损伤的药物。