Berberine, an isoquinoline alkaloid, inhibits melanoma cancer cell migration by reducing the expressions of cyclooxygenase-2, prostaglandin E2 and prostaglandin E2 receptors (Retracted article. See vol. 39, pg. 738, 2018)
Berberine, an isoquinoline alkaloid, inhibits melanoma cancer cell migration by reducing the expressions of cyclooxygenase-2, prostaglandin E2 and prostaglandin E2 receptors (Retracted article. See vol. 39, pg. 738, 2018)
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DOI：
10.1093/carcin/bgq215
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发表时间：
2011-01-01
期刊：
影响因子：
4.7
通讯作者：
Katiyar, Santosh K.
中科院分区：
文献类型：
--
作者：
Singh, Tripti;Vaid, Mudit;Katiyar, Santosh K.
黑色素瘤是皮肤病死亡的主要原因，这在很大程度上是由于其转移的倾向。我们已经研究了小檗碱，异喹啉生物碱，对人黑色素瘤癌细胞迁移的影响和这些影响的分子机制，使用黑色素瘤细胞系，A375和Hs 294。利用体外细胞迁移实验，我们发现过表达环氧化酶（考克斯）-2及其代谢产物前列腺素E-2（PGE（2））和PGE（2）受体促进细胞迁移。我们发现小檗碱处理A375和Hs 294细胞导致这些细胞迁移的浓度依赖性抑制，这与考克斯-2、PGE（2）和PGE（2）受体（EP 2和EP 4）水平的降低有关。用考克斯-2抑制剂塞来昔布处理细胞，或用考克斯-2小干扰RNA瞬时转染细胞，也抑制细胞迁移。用考克斯-2或PGE（2）的诱导剂12-O-十四酰基佛波醇-13-乙酸酯（TPA）处理细胞，可增强细胞迁移，而小檗碱可抑制TPA或PGE（2）促进的细胞迁移。小檗碱降低基础水平以及PGE（2）刺激的EP 2和EP 4表达水平。用EP 4激动剂处理细胞刺激细胞迁移，小檗碱阻断EP 4激动剂诱导的细胞迁移活性。此外，小檗碱抑制核因子-κ B（NE-κ B），考克斯-2的上游调节剂，在A375细胞的激活，和咖啡酸苯乙酯，NE-κ B的抑制剂，细胞的治疗，抑制细胞迁移。总之，这些结果首次表明，小檗碱通过抑制考克斯-2、PGE（2）和PGE（2）受体抑制黑色素瘤细胞迁移，这是侵袭和转移的一个重要步骤。
Melanoma is the leading cause of death from skin disease due, in large part, to its propensity to metastasize. We have examined the effect of berberine, an isoquinoline alkaloid, on human melanoma cancer cell migration and the molecular mechanisms underlying these effects using melanoma cell lines, A375 and Hs294. Using an in vitro cell migration assay, we show that over expression of cyclooxygenase (COX)-2, its metabolite prostaglandin E-2 (PGE(2)) and PGE(2) receptors promote the migration of cells. We found that treatment of A375 and Hs294 cells with berberine resulted in concentration-dependent inhibition of migration of these cells, which was associated with a reduction in the levels of COX-2, PGE(2) and PGE(2) receptors (EP2 and EP4). Treatment of cells with celecoxib, a COX-2 inhibitor, or transient transfection of cells with COX-2 small interfering RNA, also inhibited cell migration. Treatment of the cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), an inducer of COX-2 or PGE(2), enhanced cell migration, whereas berberine inhibited TPA- or PGE(2)-promoted cell migration. Berberine reduced the basal levels as well as PGE(2)-stimulated expression levels of EP2 and EP4. Treatment of the cells with the EP4 agonist stimulated cell migration and berberine blocked EP4 agonist-induced cell migration activity. Moreover, berberine inhibited the activation of nuclear factor-kappa B (NE-kappa B), an upstream regulator of COX-2, in A375 cells, and treatment of cells with caffeic acid phenethyl ester, an inhibitor of NE-kappa B, inhibited cell migration. Together, these results indicate for the first time that berberine inhibits melanoma cell migration, an essential step in invasion and metastasis, by inhibition of COX-2, PGE(2) and PGE(2) receptors.