Mitochondria-Targeted Honokiol Confers a Striking Inhibitory Effect on Lung Cancer via Inhibiting Complex I Activity.
Mitochondria-Targeted Honokiol Confers a Striking Inhibitory Effect on Lung Cancer via Inhibiting Complex I Activity.
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DOI：
10.1016/j.isci.2018.04.013
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发表时间：
2018-05-25
期刊：
影响因子：
5.8
通讯作者：
You M
中科院分区：
文献类型：
--
作者：
Pan J;Lee Y;Cheng G;Zielonka J;Zhang Q;Bajzikova M;Xiong D;Tsaih SW;Hardy M;Flister M;Olsen CM;Wang Y;Vang O;Neuzil J;Myers CR;Kalyanaraman B;You M
我们合成了一种靶向HNK（Mito-HNK），促进其线粒体积累;这显著增加了其在体外对高转移性肺癌细胞系以及体内原位肺肿瘤异种移植物和脑转移瘤的效力和功效。Mito-HNK在抑制细胞增殖、抑制线粒体复合物增殖、刺激活性氧产生、氧化线粒体过氧化物氧还蛋白-3和抑制mitoSTAT 3磷酸化方面的效力是HNK的>100倍。在小鼠的肺癌脑转移瘤中，Mito-HNK诱导细胞死亡的介质并减少支持侵袭和增殖的途径。相反，在非恶性间质中，Mito-HNK抑制支持转移性病变的途径，包括参与炎症和血管生成的途径。Mito-HNK显示无毒性，并靶向原发性和转移性肺癌的代谢脆弱性。它在脑中的显著抗侵袭和抗转移作用特别有趣，因为这些患者单独或与标准化疗药物联合使用的治疗选择很少。Mito-HNK抑制线粒体复合物I，并刺激氧化过氧化物氧还蛋白-3 Mito-HNK抑制mitoSTAT 3的磷酸化Mito-HNK对肺癌及其脑转移具有显著的活性天然产物化学;免疫学;药用和芳香植物
We synthesized a mitochondria-targeted honokiol (Mito-HNK) that facilitates its mitochondrial accumulation; this dramatically increases its potency and efficacy against highly metastatic lung cancer lines in vitro, and in orthotopic lung tumor xenografts and brain metastases in vivo. Mito-HNK is >100-fold more potent than HNK in inhibiting cell proliferation, inhibiting mitochondrial complex ǀ, stimulating reactive oxygen species generation, oxidizing mitochondrial peroxiredoxin-3, and suppressing the phosphorylation of mitoSTAT3. Within lung cancer brain metastases in mice, Mito-HNK induced the mediators of cell death and decreased the pathways that support invasion and proliferation. In contrast, in the non-malignant stroma, Mito-HNK suppressed pathways that support metastatic lesions, including those involved in inflammation and angiogenesis. Mito-HNK showed no toxicity and targets the metabolic vulnerabilities of primary and metastatic lung cancers. Its pronounced anti-invasive and anti-metastatic effects in the brain are particularly intriguing given the paucity of treatment options for such patients either alone or in combination with standard chemotherapeutics. Synthesis of mitochondria-targeted honokiol (Mito-HNK); Mito-HNK inhibits mitochondrial complex I, and stimulates oxidizing peroxiredoxin-3 Mito-HNK suppresses the phosphorylation of mitoSTAT3 Mito-HNK has pronounced activity against lung cancer and its brain metastases Natural Product Chemistry; Immunology; Medicinal and Aromatic Plants
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影响因子：
8.8
作者：
Cheng, G.;Zielonka, J.;McAllister, D.;Tsai, S.;Dwinell, M. B.;Kalyanaraman, B.
通讯作者：
Kalyanaraman, B.
影响因子：
3.7
作者：
Li Hd;Huang C;Huang Kj;Wu Wd;Jiang T;Cao J;Feng Zz;Qiu Zj
通讯作者：
Qiu Zj
二甲双胍通过下调 Stat3 信号促进食管鳞状细胞癌自噬和凋亡
影响因子：
9
作者：
通讯作者：
--
影响因子：
4.8
作者：
Debidda, M;Wang, L;Zheng, Y
通讯作者：
Zheng, Y
DOI：
10.1073/pnas.0404100101
发表时间：
2004-07-20
影响因子：
11.1
作者：
Dechow, TN;Pedranzini, L;Bromberg, JF
通讯作者：
Bromberg, JF