Chair and Department of Pharmacognosy with Medicinal Plant Unit, Medical University of Lublin, Lublin, Poland.
Department of Cell Biology, Maria Curie-Sklodowska University, Lublin, Poland.
J Ethnopharmacol. 2017 Jul 31;207:19-29. doi: 10.1016/j.jep.2017.06.010. Epub 2017 Jun 13.
8-methoxypsoralen (8-MOP) is a furanocoumarin and an active compound of a traditional Egyptian medicinal plant Ammi majus L, whose juice/fruit has been used for many years in folk phototherapy for the treatment of vitiligo or a hyperproliferative skin disorder, psoriasis. 8-MOP together with UVA light is also used as an anticancer drug for the treatment of cutaneous T-cell lymphoma. However, furanocoumarins exert anticancer activity even without UV irradiation.
Evaluation UV-independent anticancer activity of 8-MOP in human cancer cell lines and identification of the mechanisms involved in this action. Results could provide new data about a potential role of 8-MOP in prevention and growth suppression in a broad spectrum of cancers.
8-MOP (99%, HPLC/MS assay) was isolated from A. majus fruits by chromatographic methods. The effect of 8-MOP on cell viability was evaluated by the MTT test in several human cancer cell lines. Anti-proliferative activity of 8-MOP was evaluated by the BrdU assay in neuroblastoma (SK-N-AS) and metastatic colon cancer (SW620) cells. The Hoechst/PI staining was used for morphological analysis of cell death. An annexin V-FITC/PI double labelling and Cell Death Detection ELISA kit were used to detect apoptosis. The expression of apoptosis-associated proteins and the AKT activation status were determined by Western blot analysis.
8-MOP inhibited cell growth in several cancer cell lines. The SK-N-AS and SW620 cells were the most sensitive to the compound. 8-MOP reduced the phosphorylation of AKT, decreased the expression of Bcl-2, increased the Bax protein level, and activated caspases -8, -9, and -3 in both cell lines.
8-MOP impairs the PI3K/AKT signalling pathway and, independently of photoactivation, can inhibit the growth of neuroblastoma and colon cancer cells by induction of apoptosis via intrinsic and extrinsic pathways.
8-甲氧基补骨脂素（8-MOP）是一种呋喃香豆素，也是传统埃及药用植物 Ammi majus L 的活性化合物，其汁液/果实多年来一直用于民间光疗，治疗白癜风或增生性皮肤病，银屑病。8-MOP 与 UVA 光一起也被用作治疗皮肤 T 细胞淋巴瘤的抗癌药物。然而，呋喃香豆素即使没有紫外线照射也具有抗癌活性。
评估 8-MOP 在人癌细胞系中的非紫外线依赖性抗癌活性，并确定其作用涉及的机制。研究结果可以为 8-MOP 在广泛的癌症中预防和生长抑制的潜在作用提供新的数据。
8-MOP（HPLC/MS 测定，99%）通过色谱方法从 A. majus 果实中分离得到。MTT 试验评估 8-MOP 对几种人癌细胞系细胞活力的影响。BrdU 试验评估 8-MOP 对神经母细胞瘤（SK-N-AS）和转移性结肠癌（SW620）细胞的抗增殖活性。Hoechst/PI 染色用于细胞死亡的形态学分析。使用 Annexin V-FITC/PI 双重标记和细胞死亡检测 ELISA 试剂盒检测细胞凋亡。通过 Western blot 分析测定凋亡相关蛋白的表达和 AKT 激活状态。
8-MOP 抑制几种癌细胞系的细胞生长。SK-N-AS 和 SW620 细胞对该化合物最敏感。8-MOP 降低 AKT 的磷酸化水平，降低 Bcl-2 的表达水平，增加 Bax 蛋白水平，并在两种细胞系中激活 caspase-8、-9 和 -3。
8-MOP 损害 PI3K/AKT 信号通路，并且可以通过内在和外在途径诱导细胞凋亡，从而独立于光活化抑制神经母细胞瘤和结肠癌细胞的生长。
