Hemidesmus indicus induces apoptosis via proteasome inhibition and generation of reactive oxygen species

Hemidesmus indicus induces apoptosis via proteasome inhibition and generation of reactive oxygen species
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DOI:
10.1038/s41598-019-43609-5
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发表时间:
2019-05-10
期刊:
影响因子:
4.6
通讯作者:
Fimognari, Carmela
Fimognari, Carmela
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Turrini, Eleonora;Catanzaro, Elena;Fimognari, Carmela

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蛋白酶体抑制是一种重要的抗癌策略。在这里,我们研究了 Hemidesmus indicus(一种具有复杂抗癌活性的植物)标准化煎剂的促凋亡活性的机制,并探讨了其对人类白血病细胞中蛋白酶体活性的抑制作用。此外,我们在由单层分化的 Caco2 细胞组成的人肠上皮模型上初步测试了一些 H. indicus 植物化学物质对白血病细胞的细胞毒性及其肠道吸收。我们观察到 H. indicus 具有有效的抗白血病作用,这可归因于蛋白质和 mRNA 水平上不同关键靶标的调节以及 265 蛋白酶体表达的减少。我们发现H. indicus煎剂的一些植物标志物可以穿过肠上皮细胞单层。总的来说,我们的研究支持了 H. indicus 的药理学潜力,它可以代表肿瘤学领域的一种有趣的植物药物。
Proteasome inhibition represents an important anticancer strategy. Here, we studied the mechanisms at the basis of the pro-apoptotic activity of the standardized decoction of Hemidesmus indicus, a plant evoking a complex anticancer activity, and explored its inhibition of proteasome activity in human leukemia cells. Additionally, we preliminary tested the cytotoxicity of some H. indicus's phytochemicals on leukemia cells and their intestinal absorption on a human intestinal epithelium model consisting of a monolayer of differentiated Caco2 cells. We observed a potent antileukemic effect for H. indicus, imputable to the modulation of different critical targets at protein and mRNA levels and the reduction of the 265 proteasome expression. We found that some phytomarkers of H. indicus decoction passed through the enterocyte monolayer. Overall, our study supports the pharmacological potential of H. indicus, which can represent an interesting botanical drug in the oncological area.