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Invest New Drugs. 2021 Dec;39(6):1523-1537. doi: 10.1007/s10637-021-01137-y. Epub 2021 Jul 02.

Network pharmacology of triptolide in cancer cells: implications for transcription factor binding.

Investigational new drugs

Ean-Jeong Seo, Mona Dawood, Annika K Hult, Martin L Olsson, Thomas Efferth

Affiliations

  1. Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128, Mainz, Germany.
  2. Department of Molecular Biology, Faculty of Medical Laboratory Sciences, Al-Neelain University, Khartoum, Sudan.
  3. Division of Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, 221 84, Lund, Sweden.
  4. Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128, Mainz, Germany. [email protected].

PMID: 34213719 PMCID: PMC8541937 DOI: 10.1007/s10637-021-01137-y

Abstract

Background Triptolide is an active natural product, which inhibits cell proliferation, induces cell apoptosis, suppresses tumor metastasis and improves the effect of other therapeutic treatments in several cancer cell lines by affecting multiple molecules and signaling pathways, such as caspases, heat-shock proteins, DNA damage and NF-ĸB. Purpose We investigated the effect of triptolide towards NF-ĸB and GATA1. Methods We used cell viability assay, compare and cluster analyses of microarray-based mRNA transcriptome-wide expression data, gene promoter binding motif analysis, molecular docking, Ingenuity pathway analysis, NF-ĸB reporter cell assay, and electrophoretic mobility shift assay (EMSA) of GATA1. Results Triptolide inhibited the growth of drug-sensitive (CCRF-CEM, U87.MG) and drug-resistant cell lines (CEM/ADR5000, U87.MGΔEGFR). Hierarchical cluster analysis showed six major clusters in dendrogram. The sensitive and resistant cell lines were statistically significant (p = 0.65 × 10

© 2021. The Author(s).

Keywords: Microarrays; Natural products; Network pharmacology; Phytochemicals; Precision medicine

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