Marine sponge-derived smenospongine preferentially eliminates breast cancer stem-like cells via p38/AMPKα pathways.
Marine sponge-derived smenospongine preferentially eliminates breast cancer stem-like cells via p38/AMPKα pathways.
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海洋海绵来源的小海绵素通过 p38/AMPK α 途径优先消除乳腺癌干样细胞
DOI：
10.1002/cam4.1640
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发表时间：
2018-08
期刊：
影响因子：
4
通讯作者：
Lin H
中科院分区：
文献类型：
--
作者：
Tang J;Wu W;Yang F;Liu L;Yang Z;Liu L;Tang W;Sun F;Lin H
乳腺癌干细胞（CSCs）被认为是导致乳腺癌治疗失败的原因。有效靶向乳腺癌干细胞的新型药物迫切需要被发现以克服癌症复发和转移。我们最近通过在乳腺癌细胞中异位表达Nanog（一种核心多能性因子）建立了CSC样模型，并验证了诱导的CSC样（MCF 7-Nanog）模型获得了干细胞样特性。使用该模型，我们发现，从海绵Spongia pertusa Escherichia中分离的天然倍半萜氨基醌smenospongine（Sme）通过增加p38和AMPKα的磷酸化水平诱导G 0/G1期阻滞和内源性凋亡来优先抑制诱导的CSC样细胞增殖。重要的是，Sme表现出消除CSC样细胞的能力，这些细胞与包括Nanog、Sox 2和Bmi 1在内的干细胞标志物的下调相关。在功能上，Sme抑制MCF 7-Nanog细胞在体外形成肿瘤球和在体内发展肿瘤的能力。在Sme处理的小鼠异种移植肿瘤模型中观察到显著的抗肿瘤作用，对小鼠无明显毒性。总之，我们的研究结果提供了一个CSC样模型，以确定新型CSC靶向药物，并将Sme确定为治疗乳腺癌的候选天然药物。
Breast cancer stem cells (CSCs) have been postulated as responsible for therapeutic failure of breast cancer. Novel agents effectively targeting breast CSCs are urging to be discovered to overcome cancer relapse and metastasis. We recently established a CSC‐like model through ectopic expression Nanog, a core pluripotency factor, in breast cancer cells and validated induced CSC‐like (MCF7‐Nanog) model acquired stem‐like properties. Using this model, we found that smenospongine (Sme), a natural sesquiterpene aminoquinone isolated from marine sponge Spongia pertusa Esper, preferentially inhibited the induced CSC‐like cells proliferation by inducing G0/G1 arrest and intrinsic apoptosis via increasing the phosphorylation level of p38 and AMPKα. Importantly, Sme exhibited the ability to abrogate CSC‐like cells associated with a downregulation of stem cell markers including Nanog, Sox2, and Bmi1. Functionally, Sme inhibited the ability of MCF7‐Nanog cells to form tumor sphere in vitro and develop tumor in vivo. Significant antitumor effects are observed in Sme‐treated mouse xenograft tumor models, with no apparent toxicity to mice. Taken together, our findings provide a CSC‐like model to identify novel CSC‐targeting drugs and identify Sme as a candidate natural agent for treatment of breast cancer.
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影响因子：
64.5
作者：
Mitsui, K;Tokuzawa, Y;Yamanaka, S
通讯作者：
Yamanaka, S
影响因子：
7.4
作者：
Fillmore, Christine M.;Kuperwasser, Charlotte
通讯作者：
Kuperwasser, Charlotte
通过植物化学物质靶向癌症干细胞和信号通路：乳腺癌治疗的新方法。
影响因子：
14.5
作者：
Dandawate PR;Subramaniam D;Jensen RA;Anant S
通讯作者：
Anant S
影响因子：
2.8
作者：
Hirsch, Gabriela E.;Parisi, Mariana M.;Guma, Fatima T. C. R.
通讯作者：
Guma, Fatima T. C. R.
影响因子：
2.3
作者：
Aoki, S;Kong, D;Kobayashi, M
通讯作者：
Kobayashi, M