Tong Qiang-Song, Jiang Guo-Song, Zheng Li-Duan, Tang Shao-Tao, Cai Jia-Bin, Liu Yuan, Zeng Fu-Qing, Dong Ji-Hua
Department of Surgery, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
Anticancer Drugs. 2008 Jul;19(6):573-81. doi: 10.1097/CAD.0b013e3282fc46b0.
Recent evidence indicates that methyl jasmonate, a plant stress hormone, exhibits anticancer activity on human cancer cells. Whether methyl jasmonate could inhibit the growth of human neuroblastoma cells still, however, remains largely unknown. In this study, administration of methyl jasmonate to cultured neuroblastoma cell lines, SK-N-SH and BE(2)-C, resulted in a decrease of cell viability in a dose-dependent and time-dependent manner as demonstrated by MTT colorimetry and colony formation assay. The results from RT-PCR indicated that the expression of proliferating cell nuclear antigen, but not of cyclin D1, was downregulated by methyl jasmonate. Accordingly, the cell cycle of methyl jasmonate-treated neuroblastoma cells was arrested at the G0/G1 phase. Moreover, incubation of SK-N-SH and BE(2)-C cells with methyl jasmonate resulted in characteristic changes of apoptosis, as demonstrated by acridine orange-ethidium bromide (AO/EB) staining, Hoechst 33258 staining and flow cytometry. Moreover, methyl jasmonate decreased the expression of the X-linked inhibitor of apoptosis protein and survivin, critical members of the inhibitors of apoptosis protein family, in neuroblastoma cells. These findings indicate that methyl jasmonate suppresses the growth of cultured human neuroblastoma cells associated with downregulation of proliferating cell nuclear antigen, and induces apoptosis accompanied by downregulation of the X-linked inhibitor of apoptosis protein and survivin, which lays the groundwork for further investigation into the mechanisms of methyl jasmonate-mediated anticancer activities.
最近的证据表明，茉莉酸甲酯这种植物应激激素对人类癌细胞具有抗癌活性。然而，茉莉酸甲酯是否能抑制人类神经母细胞瘤细胞的生长在很大程度上仍然未知。在本研究中，对培养的神经母细胞瘤细胞系SK-N-SH和BE(2)-C施用茉莉酸甲酯，通过MTT比色法和集落形成试验表明，细胞活力以剂量和时间依赖性方式降低。RT-PCR结果表明，茉莉酸甲酯下调增殖细胞核抗原的表达，但不影响细胞周期蛋白D1的表达。因此，经茉莉酸甲酯处理的神经母细胞瘤细胞的细胞周期停滞在G0/G1期。此外，用茉莉酸甲酯孵育SK-N-SH和BE(2)-C细胞会导致细胞凋亡的特征性变化，吖啶橙-溴化乙锭（AO/EB）染色、Hoechst 33258染色和流式细胞术均证明了这一点。此外，茉莉酸甲酯降低了神经母细胞瘤细胞中凋亡抑制蛋白家族的关键成员——X连锁凋亡抑制蛋白和生存素的表达。这些发现表明，茉莉酸甲酯通过下调增殖细胞核抗原抑制培养的人类神经母细胞瘤细胞的生长，并通过下调X连锁凋亡抑制蛋白和生存素诱导细胞凋亡，这为进一步研究茉莉酸甲酯介导的抗癌活性机制奠定了基础。
