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Pulveraven A from the fruiting bodies of Pulveroboletus ravenelii induces apoptosis in breast cancer cell via extrinsic apoptotic signaling pathway
The Journal of Antibiotics ( IF 2.1 ) Pub Date : 2021-06-25 , DOI: 10.1038/s41429-021-00435-0
Dahae Lee 1 , Jae Sik Yu 2 , Rhim Ryoo 3 , Jin-Chul Kim 4 , Tae Su Jang 5 , Ki Sung Kang 1 , Ki Hyun Kim 2
Affiliation  

Pulveroboletus ravenelii (Beck. et Curt.) Murr. (Boletaceae), commonly known as Ravenel’s bolete, is an edible and medicinal mushroom, and is also used for preparing mushroom-based dyes. As part of a continuing project to discover the bioactive natural products from wild mushrooms, we analyzed the methanol (MeOH) extract of P. ravenelii to identify metabolites with the anticancer activity. Chemical analysis of the MeOH extract combined with liquid chromatography–mass spectrometry (LC–MS) analysis led to the isolation of a phenolic compound, pulveraven A (PA), whose chemical structure was determined using a combination of 1D and 2D NMR and LC–MS analysis. In the present study, we investigated the cytotoxicity and anticancer mechanisms of pulveraven A using human breast cancer (MCF-7) cells, and demonstrated that it reduced cell viability of MCF-7 cells below 50% (71.74 ± 3.61 μM). Annexin V Alexa Fluor 488 binding assay and western blot results revealed that pulveraven A induced apoptotic cell death via the extrinsic apoptosis pathway, as indicated by the activation of initiator caspase-8 and executioner caspase-7. Furthermore, it was accompanied by an increase in the Bax/Bcl-2 ratio. These results suggest that pulveraven A induces apoptosis in breast cancer cells via the extrinsic apoptotic signaling pathway.



中文翻译:

Pulveroboletus ravenelii 子实体中的 Pulveraven A 通过外源性凋亡信号通路诱导乳腺癌细胞凋亡

Pulveroboletus ravenelii (Beck. et Curt.) Murr。(牛肝菌科),俗称罗芙奥牛肝菌,是一种药食兼用的蘑菇,也用于制备蘑菇基染料。作为从野生蘑菇中发现生物活性天然产物的持续项目的一部分,我们分析了P. ravenelii的甲醇 (MeOH) 提取物鉴定具有抗癌活性的代谢物。MeOH 提取物的化学分析与液相色谱-质谱 (LC-MS) 分析相结合,导致酚类化合物 pulveraven A (PA) 的分离,其化学结构是使用 1D 和 2D NMR 和 LC 的组合确定的-质谱分析。在本研究中,我们使用人乳腺癌 (MCF-7) 细胞研究了 pulveraven A 的细胞毒性和抗癌机制,并证明它可将 MCF-7 细胞的细胞活力降低至 50% (71.74 ± 3.61 μM) 以下。Annexin V Alexa Fluor 488 结合测定和蛋白质印迹结果表明,pulveraven A 通过外在凋亡途径诱导凋亡细胞死亡,如启动子 caspase-8 和刽子手 caspase-7 的激活所示。此外,它伴随着 Bax/Bcl-2 比率的增加。这些结果表明,pulveraven A 通过外源性凋亡信号通路诱导乳腺癌细胞凋亡。

更新日期:2021-06-25
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