Blocking autophagy enhances the apoptotic effect of 18β-glycyrrhetinic acid on human sarcoma cells via endoplasmic reticulum stress and JNK activation.
Blocking autophagy enhances the apoptotic effect of 18β-glycyrrhetinic acid on human sarcoma cells via endoplasmic reticulum stress and JNK activation.
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阻断自噬通过内质网应激和 JNK 激活增强 18β-甘草次酸对人肉瘤细胞的凋亡作用
DOI：
10.1038/cddis.2017.441
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发表时间：
2017-09-21
影响因子：
9
通讯作者：
Fan S
中科院分区：
文献类型：
--
作者：
Shen S;Zhou M;Huang K;Wu Y;Ma Y;Wang J;Ma J;Fan S
肉瘤是一种罕见的癌症，与常见的癌症不同，它发生在不同类型的组织中。18β-甘草次酸（GA）是一种新型的天然衍生药物，已被证明在多种癌症中具有有效的抗肿瘤作用。然而，GA对人肉瘤的作用及其潜在机制仍有待阐明。在目前的研究中，我们发现GA通过诱导G0/ g1期阻滞抑制肉瘤细胞增殖。暴露于GA导致caspase-3、-8和9的激活，表明GA通过外源性和内在途径诱导细胞凋亡。此外，以LC3-I向LC3-II转化为特征的自噬途径被激活，导致Beclin-1蛋白水平升高，p62表达降低，自噬通量刺激。本研究结果表明，GA通过IRE1-JNK通路诱导内质网（ER）应激，从而刺激自噬。当自噬途径被特定的化学抑制剂阻断时，我们的数据支持ga诱导的自噬的促生存作用。最后，GA在体内显著减少了肉瘤的生长，几乎没有器官相关的毒性。目前的结果表明，GA与特异性自噬抑制剂的联合治疗是治疗肉瘤的一种有希望的治疗方法。
Sarcoma, a rare form of cancer, is unlike the much more common carcinomas as it occurs in a distinct type of tissue. The potent antitumor effects of 18β-glycyrrhetinic acid (GA), a novel naturally derived agent, have been demonstrated in various cancers. However, the effect of GA on human sarcoma, and the underlying mechanisms, remain to be elucidated. In the current study, we show that GA inhibits sarcoma cell proliferation by inducing G0/G1-phase arrest. Exposure to GA resulted in the activation of caspase-3,-8, and-9, indicating that GA induced apoptosis through both extrinsic and intrinsic pathways. In addition, the autophagy pathway, characterized by the conversion of LC3-I to LC3-II, was activated, resulting in increased Beclin-1 protein levels, decreased p62 expression, and stimulation of autophagic flux. The present findings showed that GA stimulated autophagy by inducing endoplasmic reticulum (ER) stress via the IRE1–JNK pathway. Our data supported the prosurvival role of GA-induced autophagy when the autophagy pathway was blocked with specific chemical inhibitors. Finally, GA markedly reduced sarcoma growth, with little organ-related toxicity, in vivo. The present results suggest that the combination of GA with a specific autophagy inhibitor represents a promising therapeutic approach for the treatment of sarcoma.
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DOI：
10.1073/pnas.251194298
发表时间：
2001-11-20
影响因子：
11.1
作者：
Bennett, BL;Sasaki, DT;Anderson, DW
通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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光催化氧化去除室内挥发性有机化合物：简要回顾与展望
DOI：
10.3390/molecules21010056
发表时间：
2016-01-04
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Huang Y;Ho SS;Lu Y;Niu R;Xu L;Cao J;Lee S
通讯作者：
Lee S