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黄皮酰胺及其生物活性成分诺卡酮对结直肠癌细胞的抗增殖活性。

Anti-proliferative activity of A. Oxyphylla and its bioactive constituent nootkatone in colorectal cancer cells.

机构信息

Department of Veterinary Medicine, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, 08826, South Korea.

Department of Otolaryngology-Head and Neck Surgery, Research Institute and Hospital, National Cancer Center, Goyang, South Korea.

出版信息

BMC Cancer. 2020 Sep 14;20(1):881. doi: 10.1186/s12885-020-07379-y.

DOI:10.1186/s12885-020-07379-y
PMID:32928152
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7491188/
Abstract

BACKGROUND

A. oxyphylla extract is known to possess a wide range of pharmacological activites. However, the molecular mechanism of A. oxyphylla and its bioactive compound nootkatone in colorectal cancer is unknown.

METHODS

Our study aims to examine the role of A. oxyphylla and its bioactive compound nootkatone, in tumor suppression using several in vitro assays.

RESULTS

Both A. oxyphylla extract and nootkatone exhibited antiproliferative activity in colorectal cancer cells. A. oxyphylla displayed antioxidant activity in colorectal cancer cells, likely mediated via induction of HO-1. Furthermore, expression of pro-apoptotic protein NAG-1 and cell proliferative protein cyclin D1 were increased and decreased respectively in the presence of A. oxyphylla. When examined for anticancer activity, nootkatone treatment resulted in the reduction of colony and spheroid formation. Correspondingly, nootkatone also led to increased NAG-1 expression and decreased cyclin D1 expression. The mechanism by which nootkatone suppresses cyclin D1 involves protein level regulation, whereas nootkatone increases NAG-1 expression at the transcriptional level. In addition to having PPARγ binding activity, nootkatone also increases EGR-1 expression which ultimately results in enhanced NAG-1 promoter activity.

CONCLUSION

In summary, our findings suggest that nootkatone is an anti-tumorigenic compound harboring antiproliferative and pro-apoptotic activity.

摘要

背景

铁皮石斛提取物具有广泛的药理活性。然而，铁皮石斛及其生物活性化合物诺卡酮在结直肠癌中的分子机制尚不清楚。

方法

本研究旨在通过几种体外实验研究铁皮石斛及其生物活性化合物诺卡酮在肿瘤抑制中的作用。

结果

铁皮石斛提取物和诺卡酮均对结直肠癌细胞表现出增殖抑制活性。铁皮石斛在结直肠癌细胞中显示出抗氧化活性，可能通过诱导 HO-1 介导。此外，在存在铁皮石斛的情况下，促凋亡蛋白 NAG-1 和细胞增殖蛋白 cyclin D1 的表达分别增加和减少。当研究其抗癌活性时，诺卡酮处理导致集落和球体形成减少。相应地，诺卡酮还导致 NAG-1 表达增加和 cyclin D1 表达减少。诺卡酮抑制 cyclin D1 的机制涉及蛋白水平调节，而诺卡酮通过转录水平增加 NAG-1 的表达。除了具有 PPARγ 结合活性外，诺卡酮还增加 EGR-1 的表达，从而最终增强 NAG-1 启动子活性。

结论

综上所述，我们的研究结果表明，诺卡酮是一种具有抗肿瘤增殖和促凋亡活性的抗肿瘤化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94d2/7491188/a651273f2715/12885_2020_7379_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94d2/7491188/34a46aebb6ce/12885_2020_7379_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94d2/7491188/7fcc02ef573b/12885_2020_7379_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94d2/7491188/d8f14cde4703/12885_2020_7379_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94d2/7491188/eba4e4a50d26/12885_2020_7379_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94d2/7491188/4e1198e684fc/12885_2020_7379_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94d2/7491188/9a8156aabc59/12885_2020_7379_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94d2/7491188/a651273f2715/12885_2020_7379_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94d2/7491188/34a46aebb6ce/12885_2020_7379_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94d2/7491188/7fcc02ef573b/12885_2020_7379_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94d2/7491188/d8f14cde4703/12885_2020_7379_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94d2/7491188/eba4e4a50d26/12885_2020_7379_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94d2/7491188/4e1198e684fc/12885_2020_7379_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94d2/7491188/9a8156aabc59/12885_2020_7379_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94d2/7491188/a651273f2715/12885_2020_7379_Fig7_HTML.jpg

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