{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T15:14:35Z","timestamp":1775661275511,"version":"3.50.1"},"reference-count":74,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2016,4,15]],"date-time":"2016-04-15T00:00:00Z","timestamp":1460678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Drug resistance and the severe side effects of chemotherapy necessitate the development of novel anticancer drugs. Natural products are a valuable source for drug development. Scopoletin is a coumarin compound, which can be found in several Artemisia species and other plant genera. Microarray-based RNA expression profiling of the NCI cell line panel showed that cellular response of scopoletin did not correlate to the expression of ATP-binding cassette (ABC) transporters as classical drug resistance mechanisms (ABCB1, ABCB5, ABCC1, ABCG2). This was also true for the expression of the oncogene EGFR and the mutational status of the tumor suppressor gene, TP53. However, mutations in the RAS oncogenes and the slow proliferative activity in terms of cell doubling times significantly correlated with scopoletin resistance. COMPARE and hierarchical cluster analyses of transcriptome-wide mRNA expression resulted in a set of 40 genes, which all harbored binding motifs in their promoter sequences for the transcription factor, NF-\u03baB, which is known to be associated with drug resistance. RAS mutations, slow proliferative activity, and NF-\u03baB may hamper its effectiveness. By in silico molecular docking studies, we found that scopoletin bound to NF-\u03baB and its regulator I\u03baB. Scopoletin activated NF-\u03baB in a SEAP-driven NF-\u03baB reporter cell line, indicating that NF-\u03baB might be a resistance factor for scopoletin. In conclusion, scopoletin might serve as lead compound for drug development because of its favorable activity against tumor cells with ABC-transporter expression, although NF-\u03baB activation may be considered as resistance factor for this compound. Further investigations are warranted to explore the full therapeutic potential of this natural product.<\/jats:p>","DOI":"10.3390\/molecules21040496","type":"journal-article","created":{"date-parts":[[2016,4,15]],"date-time":"2016-04-15T11:36:02Z","timestamp":1460720162000},"page":"496","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Pharmacogenomics of Scopoletin in Tumor Cells"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5377-6548","authenticated-orcid":false,"given":"Ean-Jeong","family":"Seo","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Staudinger Weg 5, 55128 Mainz, Germany"}]},{"given":"Mohamed","family":"Saeed","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Staudinger Weg 5, 55128 Mainz, Germany"}]},{"given":"Betty","family":"Law","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China"}]},{"given":"An","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China"}]},{"given":"Onat","family":"Kadioglu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Staudinger Weg 5, 55128 Mainz, Germany"}]},{"given":"Henry","family":"Greten","sequence":"additional","affiliation":[{"name":"Abel Salazar Biomedical Sciences Institute, University of Porto, Porto 4099-002, Portugal"},{"name":"Heidelberg School of Chinese Medicine, Heidelberg 69126, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3266-4050","authenticated-orcid":false,"given":"Thomas","family":"Efferth","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Staudinger Weg 5, 55128 Mainz, Germany"}]}],"member":"1968","published-online":{"date-parts":[[2016,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3136","DOI":"10.2174\/092986711796391570","article-title":"Inhibition of tumor angiogenesis by antibodies, synthetic small molecules and natural products","volume":"18","author":"Wahl","year":"2011","journal-title":"Curr. 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