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癌细胞中抗坏血酸与姜黄素两种主要代谢产物组合的药物基因组学特征及等效线图分析

Pharmacogenomic Characterization and Isobologram Analysis of the Combination of Ascorbic Acid and Curcumin-Two Main Metabolites of -in Cancer Cells.

作者信息

Ooko Edna, Kadioglu Onat, Greten Henry J, Efferth Thomas

机构信息

Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University Mainz, Germany.

Heidelberg School of Chinese MedicineHeidelberg, Germany; Abel Salazar Biomedical Sciences Institute, University of PortoPorto, Portugal.

出版信息

Front Pharmacol. 2017 Feb 2;8:38. doi: 10.3389/fphar.2017.00038. eCollection 2017.

DOI:10.3389/fphar.2017.00038
PMID:28210221
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5288649/
Abstract

has long been used in China and India as anti-inflammatory agent to treat a wide variety of conditions and also as a spice for varied curry preparations. The chemoprofile of the species exhibits the presence of varied phytochemicals with curcumin being present in all three species but AA only being shown in . This study explored the effect of a curcumin/AA combination on human cancer cell lines. The curcumin/AA combination was assessed by isobologram analysis using the Loewe additivity drug interaction model. The drug combination showed additive cytotoxicity toward CCRF-CEM and CEM/ADR5000 leukemia cell lines and HCT116p53 and HCT116p53 colon cancer cell line, while the glioblastoma cell lines U87MG and U87MG.ΔEGFR showed additive to supra-additive cytotoxicity. Gene expression profiles predicting sensitivity and resistance of tumor cells to induction by curcumin and AA were determined by microarray-based mRNA expressions, COMPARE, and hierarchical cluster analyses. Numerous genes involved in transcription (), apoptosis-regulation () signal transduction () DNA repair (), mRNA metabolism (), and transporter genes () correlated with cellular responsiveness to curcumin and ascorbic acid. In conclusion, this study shows the effect of the curcumin/AA combination and identifies several candidate genes that may regulate the response of varied cancer cells to curcumin and AA.

摘要

长期以来，它在中国和印度一直被用作抗炎剂来治疗多种病症，也被用作各种咖喱制品的香料。该物种的化学特征显示存在多种植物化学物质，姜黄素在所有三个物种中都有，但抗坏血酸仅在[具体物种]中显示。本研究探讨了姜黄素/抗坏血酸组合对人癌细胞系的影响。使用洛氏加和性药物相互作用模型通过等效线图分析评估姜黄素/抗坏血酸组合。该药物组合对CCRF - CEM和CEM/ADR5000白血病细胞系以及HCT116p53和HCT116p53结肠癌细胞系显示出相加细胞毒性，而对胶质母细胞瘤细胞系U87MG和U87MG.ΔEGFR显示出相加至超相加细胞毒性。通过基于微阵列的mRNA表达、COMPARE和层次聚类分析确定了预测肿瘤细胞对姜黄素和抗坏血酸诱导的敏感性和抗性的基因表达谱。许多参与转录（[具体基因数]）、凋亡调节（[具体基因数]）、信号转导（[具体基因数]）、DNA修复（[具体基因数]）、mRNA代谢（[具体基因数]）和转运蛋白基因（[具体基因数]）的基因与细胞对姜黄素和抗坏血酸的反应相关。总之，本研究显示了姜黄素/抗坏血酸组合的作用，并鉴定了几个可能调节不同癌细胞对姜黄素和抗坏血酸反应的候选基因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d5a/5288649/8cb2c8e5eb9a/fphar-08-00038-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d5a/5288649/18b84d446d3d/fphar-08-00038-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d5a/5288649/f51e866c4866/fphar-08-00038-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d5a/5288649/e824492279e7/fphar-08-00038-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d5a/5288649/0f6b5122d0b4/fphar-08-00038-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d5a/5288649/5f25710fafa7/fphar-08-00038-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d5a/5288649/9595dfe75e06/fphar-08-00038-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d5a/5288649/8cb2c8e5eb9a/fphar-08-00038-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d5a/5288649/18b84d446d3d/fphar-08-00038-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d5a/5288649/f51e866c4866/fphar-08-00038-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d5a/5288649/e824492279e7/fphar-08-00038-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d5a/5288649/0f6b5122d0b4/fphar-08-00038-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d5a/5288649/5f25710fafa7/fphar-08-00038-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d5a/5288649/9595dfe75e06/fphar-08-00038-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d5a/5288649/8cb2c8e5eb9a/fphar-08-00038-g0007.jpg

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