Department of Immunology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia.
Food Chem Toxicol. 2012 Sep;50(9):3181-9. doi: 10.1016/j.fct.2012.05.047. Epub 2012 Jun 7.
Intrinsic characteristics of melanoma cells such as expression of inducible nitric oxide synthase (iNOS), redox status, and activity of signaling pathways involved in proliferation, differentiation and cell death define the response of the cells to the diverse treatments. In this context we compared the effectiveness of herbal antaquinone aloe emodin (AE) against mouse B16 melanoma and human A375, different in initial activity of ERK1/2, constitutive iNOS expression and basal level of reactive oxygen species (ROS). Both cell lines are sensitive to AE treatment. However, while the agent induces differentiation of B16 cells toward melanocytes, in A375 cells promoted massive apoptosis. Differentiation of B16 cells, characterized by enhanced melanin production and tyrosinase activity, was mediated by H(2)O(2) production synchronized with rapid p53 accumulation and enhanced expression of cyclins D1 and D3. Caspase mediated apoptosis triggered in A375 cells was accompanied with Bcl-2 but not iNOS down-regulation. In addition, opposite regulation of Akt-ERK1/2 axis in AE treated B16 and A375 cells correlated with different outcome of the treatment. However, AE in a dose-dependent manner rescued both B16 and A375 cells from doxorubicin- or paclitaxel-induced killing. These data indicate that caution is warranted when AE is administrated to the patients with conventional chemotherapy.
黑色素瘤细胞的固有特性，如诱导型一氧化氮合酶（iNOS）的表达、氧化还原状态以及参与增殖、分化和细胞死亡的信号通路的活性，决定了细胞对各种治疗方法的反应。在这种情况下，我们比较了草药安特奎酮大黄素（AE）对小鼠 B16 黑色素瘤和人 A375 的疗效，这两种细胞系在 ERK1/2 的初始活性、组成型 iNOS 表达和基础活性氧（ROS）水平方面存在差异。这两种细胞系对 AE 治疗都敏感。然而，虽然该药物诱导 B16 细胞向黑色素细胞分化，但在 A375 细胞中则促进大量细胞凋亡。B16 细胞的分化特征是黑色素生成和酪氨酸酶活性增强，这是由与 p53 快速积累和细胞周期蛋白 D1 和 D3 表达增强同步产生的 H2O2 介导的。在 A375 细胞中触发的半胱天冬酶介导的细胞凋亡伴随着 Bcl-2 但不是 iNOS 的下调。此外，AE 处理的 B16 和 A375 细胞中 Akt-ERK1/2 轴的相反调节与治疗结果的不同相关。然而，AE 以剂量依赖的方式挽救了阿霉素或紫杉醇诱导的 B16 和 A375 细胞的杀伤。这些数据表明，当 AE 用于接受常规化疗的患者时，需要谨慎。
