Zhang Ting, Sharma Alok, Li Yulong, Zhou Yaoyao, Ding Xianting
School of Biomedical Engineering, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
School of Biomedical Engineering, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
J Photochem Photobiol B. 2018 Jan;178:568-576. doi: 10.1016/j.jphotobiol.2017.12.007. Epub 2017 Dec 13.
Excessive exposure to ultraviolet (UV) B radiation may lead to skin damage, photosensitivity, or even tumorigenesis via induction of oxidative stress. Naturally derived antioxidants could play significant roles in cancer therapy due to their multi-targeted actions and lack of substantial toxicity. Drug combinations target at diverse pathway of cells and make cells export meticulous biological outcomes through the multifaceted signaling network. The UVB protective effects of combinations of naturally derived antioxidants- curcumin, resveratrol, proanthocyanidins, baicalein, and beta-nicotinamide adenine dinucleotide (NADH) were investigated. An oxidative cell damage model was established to study the ultraviolet irradiation system. An orthogonal array composite design (OACD) was employed in the optimization of antioxidants combinations. Combination of resveratrol (0.1μM) and baicalein in medium concentration (0.2μM), with NADH in high concentration (0.8μM) was found to be the most efficacious combination among all the 30 runs performed using OACD. The findings suggested that UVB exposure-inflicted cell apoptosis can be significantly reduced by naturally-derived antioxidant combinations. These results provide an insight into the discovery of synergistic antioxidant combinations in skin cancer, using orthogonal array composite design (OACD). The results also have practical implications in the understanding of drug mechanisms in skin cancer, which can assist clinical practice by recommending better drug combinations.
过度暴露于紫外线B辐射可能会通过诱导氧化应激导致皮肤损伤、光敏感甚至肿瘤发生。天然来源的抗氧化剂由于其多靶点作用且毒性不大,可能在癌症治疗中发挥重要作用。药物组合作用于细胞的不同途径,并通过多方面的信号网络使细胞产生精确的生物学结果。研究了天然来源的抗氧化剂——姜黄素、白藜芦醇、原花青素、黄芩素和β-烟酰胺腺嘌呤二核苷酸(NADH)组合的紫外线B防护效果。建立了氧化细胞损伤模型来研究紫外线照射系统。采用正交阵列复合设计(OACD)优化抗氧化剂组合。在使用OACD进行的所有30次实验中,发现白藜芦醇(0.1μM)与中等浓度(0.2μM)的黄芩素以及高浓度(0.8μM)的NADH组合是最有效的组合。研究结果表明,天然来源的抗氧化剂组合可显著减少紫外线B照射引起的细胞凋亡。这些结果为利用正交阵列复合设计(OACD)发现皮肤癌中的协同抗氧化剂组合提供了思路。这些结果对于理解皮肤癌的药物作用机制也具有实际意义,可为临床实践推荐更好的药物组合提供帮助。