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丁香水提物通过 AMPK/ULK 通路诱导自噬抑制肿瘤生长。

Aqueous extract of clove inhibits tumor growth by inducing autophagy through AMPK/ULK pathway.

机构信息

Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.

Basic Medical School, Shanxi Datong University, Datong, China.

出版信息

Phytother Res. 2019 Jul;33(7):1794-1804. doi: 10.1002/ptr.6367. Epub 2019 Apr 16.

DOI:10.1002/ptr.6367
PMID:30993793
Abstract

Cloves (Syzygium aromaticum), a traditional Chinese medicinal herb, displays broad biological activity. In the present study, the aqueous extract of clove (AEC) was prepared, and its anticancer affects were studied. 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetra-zolium (MTS) analysis revealed that AEC was able to inhibit cancer cell growth in vitro on several cancer cell lines; the IC is around 150 μg/ml for human pancreatic ASPC-1 and human colon HT-29 cancer cells. Treatment of the cancer cells with AEC also diminished the colony formation significantly in both human pancreatic ASPC-1 cancer cells and human colon HT-29 cancer cells. In vivo study revealed that AEC inhibited the tumor growth significantly in HT-29 xenograft mice model. Transmission electron microscope, flow cytometry assay, and fluorescence microscope analysis confirmed that AEC is capable of inducing cell autophagy. Further study showed that AMPK/ULK pathway plays an important role in AEC-induced autophagy in cancer cells. Analysis of AEC components was performed by liquid chromatograph mass spectrometer approach, and more than nine constitutes were identified in AEC fraction. The study provides evidence that AEC has potential to be developed as a novel anticancer agent or as an adjuvant in cancer chemotherapy.

摘要

丁香(Syzygium aromaticum)是一种传统的中药,具有广泛的生物活性。在本研究中,制备了丁香的水提取物(AEC),并研究了其抗癌作用。3-(4,5-二甲基噻唑-2-基)-5-(3-羧甲氧基苯基)-2-(4-磺苯基)-2H-四唑(MTS)分析表明,AEC 能够抑制几种癌细胞系的体外癌细胞生长;IC 约为 150μg/ml,用于人胰腺 ASPC-1 和人结肠 HT-29 癌细胞。用 AEC 处理癌细胞还显著减少了人胰腺 ASPC-1 癌细胞和人结肠 HT-29 癌细胞中的集落形成。体内研究表明,AEC 显著抑制 HT-29 异种移植小鼠模型中的肿瘤生长。透射电子显微镜、流式细胞术分析和荧光显微镜分析证实,AEC 能够诱导细胞自噬。进一步的研究表明,AMPK/ULK 通路在 AEC 诱导的癌细胞自噬中起重要作用。通过液相色谱质谱法分析 AEC 的成分,在 AEC 馏分中鉴定出超过九种成分。该研究为 AEC 具有开发为新型抗癌药物或作为癌症化疗辅助剂的潜力提供了证据。

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