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从食用蘑菇:刺芹侧耳中提取的肽可诱导人肺癌细胞凋亡。

Peptides extracted from edible mushroom: Lentinus squarrosulus induces apoptosis in human lung cancer cells.

作者信息

Prateep Arisara, Sumkhemthong Somruethai, Suksomtip Maneewan, Chanvorachote Pithi, Chaotham Chatchai

机构信息

a Department of Biochemistry and Microbiology, Faculty of Pharmaceutical Sciences , Chulalongkorn University , Bangkok , Thailand.

b Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences , Chulalongkorn University , Bangkok , Thailand.

出版信息

Pharm Biol. 2017 Dec;55(1):1792-1799. doi: 10.1080/13880209.2017.1325913.

Abstract

CONTEXT

Lentinus squarrosulus Mont. (Polyporaceae) is an interesting source of diverse bioactive compounds.

OBJECTIVE

This is the first study of the anticancer activity and underlying mechanism of peptides extracted from Lentinus squarrosuls.

MATERIALS AND METHODS

Peptides were isolated from the aqueous extract of L. squarrosulus by employing solid ammonium sulphate precipitation. They were further purified by ion-exchange chromatography on diethylaminoethanol (DEAE)-cellulose and gel filtration chromatography on Sephadex G25. Anticancer activity was investigated in human lung cancer H460, H292 and H23 cells cultured with 0-40 μg/mL of peptide extracts for 24 h. Cell viability and mode of cell death were evaluated by MTT and nuclear staining assay, respectively. Western blotting was used to investigate the alteration of apoptosis-regulating proteins in lung cancer cells treated with peptide extracts (0-20 μg/mL) for 24 h.

RESULTS

The cytotoxicity of partially-purified peptide extracts from L. squarrosulus was indicated with IC of ∼26.84 ± 2.84, 2.80 ± 2.14 and 18.84 ± 0.30 μg/mL in lung cancer H460, H292 and H23 cells, respectively. The extracts at 20 μg/mL induced apoptosis through the reduction of anti-apoptotic Bcl-2 protein (∼0.5-fold reduction) and up-regulation of BAX (∼4.5-fold induction), a pro-apoptotic protein. Furthermore, L. squarrosulus peptide extracts (20 μg/mL) also decreased the cellular level of death receptor inhibitor c-FLIP (∼0.6-fold reduction).

CONCLUSIONS AND DISCUSSION

This study provides the novel anticancer activity and mechanism of L. squarrosulus peptide extracts, which encourage further investigation and development of the extracts for anticancer use.

摘要

背景

糙皮侧耳(多孔菌科)是多种生物活性化合物的有趣来源。

目的

这是首次对从糙皮侧耳中提取的肽的抗癌活性及其潜在机制进行研究。

材料与方法

采用固体硫酸铵沉淀法从糙皮侧耳水提取物中分离肽。通过二乙氨基乙醇(DEAE)-纤维素离子交换色谱和葡聚糖凝胶G25凝胶过滤色谱进一步纯化。用0-40μg/mL的肽提取物培养人肺癌H460、H292和H23细胞24小时,研究其抗癌活性。分别通过MTT和核染色试验评估细胞活力和细胞死亡方式。用蛋白质免疫印迹法研究用肽提取物(0-20μg/mL)处理24小时的肺癌细胞中凋亡调节蛋白的变化。

结果

糙皮侧耳部分纯化的肽提取物对肺癌H460、H292和H23细胞的细胞毒性分别以IC为26.84±2.84、2.80±2.14和18.84±0.30μg/mL表示。20μg/mL的提取物通过降低抗凋亡Bcl-2蛋白(0.5倍降低)和上调促凋亡蛋白BAX(4.5倍诱导)诱导凋亡。此外,糙皮侧耳肽提取物(20μg/mL)还降低了死亡受体抑制剂c-FLIP的细胞水平(0.6倍降低)。

结论与讨论

本研究提供了糙皮侧耳肽提取物新的抗癌活性和机制,这鼓励对该提取物进行进一步的研究和开发以用于抗癌。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ee4/6130440/a6cb1d605f35/IPHB_A_1325913_F0001_C.jpg

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