Fucoidan Suppresses the Growth of Human Acute Promyelocytic Leukemia Cells In Vitro and In Vivo
Fucoidan Suppresses the Growth of Human Acute Promyelocytic Leukemia Cells In Vitro and In Vivo
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DOI：
10.1002/jcp.25119
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发表时间：
2016-03-01
影响因子：
5.6
通讯作者：
Dickinson, Joanne L.
中科院分区：
文献类型：
--
作者：
Atashrazm, Farzaneh;Lowenthal, Ray M.;Dickinson, Joanne L.
褐藻糖胶是海藻的天然成分，据报道具有免疫调节和抗肿瘤作用。支撑这些活动的机制仍然知之甚少。在这项研究中，研究了岩藻依聚糖在急性髓系白血病（AML）细胞中的细胞毒性和抗肿瘤活性。用岩藻依聚糖处理人 AML 细胞系 NB4、KG1a、HL60 和 K562，分析细胞周期、细胞增殖和凋亡途径分子的表达。褐藻糖胶通过内在和外在途径抑制急性早幼粒细胞白血病 (APL) 细胞系 NB4 和 HL60 的增殖并诱导细胞凋亡，但在 KG1a 和 K562 细胞中则不然。在 NB4 细胞中，细胞凋亡是 caspase 依赖性的，因为用泛 caspase 抑制剂预处理可显着减弱细胞凋亡。 P21/WAF1/CIP1 显着上调，导致细胞周期停滞。岩藻依聚糖通过 Thr(308) 残基而非 Ser(473) 的低磷酸化降低 ERK1/2 的激活并下调 AKT 的激活。在体内，采用使用NB4细胞的异种移植模型。给小鼠喂食岩藻依聚糖，并在接种 NB4 细胞后测量肿瘤生长。随后，还检查了脾自然杀伤（NK）细胞的细胞毒活性。口服剂量的岩藻依聚糖可显着延迟异种移植模型中的肿瘤生长并增加 NK 细胞的溶细胞活性。综上所述，这些数据表明岩藻依聚糖对 APL 细胞的选择性抑制作用及其对小鼠 APL 发育的保护作用值得进一步研究岩藻依聚糖作为治疗某些类型白血病的有用药物。 J.细胞。生理学。 231：688-697，2016 年。(c) 2015 年 Wiley 期刊公司。
Fucoidan, a natural component of seaweeds, is reported to have immunomodulatory and anti-tumor effects. The mechanisms underpinning these activities remain poorly understood. In this study, the cytotoxicity and anti-tumor activities of fucoidan were investigated in acute myeloid leukemia (AML) cells. The human AML cell lines NB4, KG1a, HL60, and K562 were treated with fucoidan and cell cycle, cell proliferation, and expression of apoptotic pathways molecules were analyzed. Fucoidan suppressed the proliferation and induced apoptosis through the intrinsic and extrinsic pathways in the acute promyelocytic leukemia (APL) cell lines NB4 and HL60, but not in KG1a and K562 cells. In NB4 cells, apoptosis was caspase-dependent as it was significantly attenuated by pre-treatment with a pan-caspase inhibitor. P21/WAF1/CIP1 was significantly up-regulated leading to cell cycle arrest. Fucoidan decreased the activation of ERK1/2 and down-regulated the activation of AKT through hypo-phosphorylation of Thr(308) residue but not Ser(473). In vivo, a xenograft model using the NB4 cells was employed. Mice were fed with fucoidan and tumor growth was measured following inoculation with NB4 cells. Subsequently, splenic natural killer (NK) cell cytotoxic activity was also examined. Oral doses of fucoidan significantly delayed tumor growth in the xenograft model and increased cytolytic activity of NK cells. Taken together, these data suggest that the selective inhibitory effect of fucoidan on APL cells and its protective effect against APL development in mice warrant further investigation of fucoidan as a useful agent in treatment of certain types of leukemia. J. Cell. Physiol. 231: 688-697, 2016. (c) 2015 Wiley Periodicals, Inc.