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Target Identification of the Marine Natural Products Dictyoceratin-A and -C as Selective Growth Inhibitors in Cancer Cells Adapted to Hypoxic Environments
Hypoxia-adapted cancer cells in tumors contribute to the pathological progression of cancer. The marine spongean sesquiterpene phenols dictyoceratin-A (1) and -C (2) have been shown to induce hypoxia-selective growth inhibition in cultured cancer cells and exhibit in vivo antitumor effects. These co...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471994/ https://www.ncbi.nlm.nih.gov/pubmed/30857246 http://dx.doi.org/10.3390/md17030163 |
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author | Kawachi, Takashi Tanaka, Shun Fukuda, Akinori Sumii, Yuji Setiawan, Andi Kotoku, Naoyuki Kobayashi, Motomasa Arai, Masayoshi |
author_facet | Kawachi, Takashi Tanaka, Shun Fukuda, Akinori Sumii, Yuji Setiawan, Andi Kotoku, Naoyuki Kobayashi, Motomasa Arai, Masayoshi |
author_sort | Kawachi, Takashi |
collection | PubMed |
description | Hypoxia-adapted cancer cells in tumors contribute to the pathological progression of cancer. The marine spongean sesquiterpene phenols dictyoceratin-A (1) and -C (2) have been shown to induce hypoxia-selective growth inhibition in cultured cancer cells and exhibit in vivo antitumor effects. These compounds inhibit the accumulation of hypoxia-inducible factor-1α (HIF-1α), which is a drug target in hypoxia-adapted cancer cells, under hypoxic conditions. However, the target molecules of compounds 1 and 2, which are responsible for decreasing HIF-1α expression under hypoxic conditions, remain unclear. In this study, we synthesized probe molecules for compounds 1 and 2 to identify their target molecules and found that both compounds bind to RNA polymerase II-associated protein 3 (RPAP3), which is a component of the R2TP/Prefoldin-like (PEDL) complex. In addition, RPAP3-knockdown cells showed a phenotype similar to that of compound-treated cells. |
format | Online Article Text |
id | pubmed-6471994 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-64719942019-04-27 Target Identification of the Marine Natural Products Dictyoceratin-A and -C as Selective Growth Inhibitors in Cancer Cells Adapted to Hypoxic Environments Kawachi, Takashi Tanaka, Shun Fukuda, Akinori Sumii, Yuji Setiawan, Andi Kotoku, Naoyuki Kobayashi, Motomasa Arai, Masayoshi Mar Drugs Article Hypoxia-adapted cancer cells in tumors contribute to the pathological progression of cancer. The marine spongean sesquiterpene phenols dictyoceratin-A (1) and -C (2) have been shown to induce hypoxia-selective growth inhibition in cultured cancer cells and exhibit in vivo antitumor effects. These compounds inhibit the accumulation of hypoxia-inducible factor-1α (HIF-1α), which is a drug target in hypoxia-adapted cancer cells, under hypoxic conditions. However, the target molecules of compounds 1 and 2, which are responsible for decreasing HIF-1α expression under hypoxic conditions, remain unclear. In this study, we synthesized probe molecules for compounds 1 and 2 to identify their target molecules and found that both compounds bind to RNA polymerase II-associated protein 3 (RPAP3), which is a component of the R2TP/Prefoldin-like (PEDL) complex. In addition, RPAP3-knockdown cells showed a phenotype similar to that of compound-treated cells. MDPI 2019-03-08 /pmc/articles/PMC6471994/ /pubmed/30857246 http://dx.doi.org/10.3390/md17030163 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kawachi, Takashi Tanaka, Shun Fukuda, Akinori Sumii, Yuji Setiawan, Andi Kotoku, Naoyuki Kobayashi, Motomasa Arai, Masayoshi Target Identification of the Marine Natural Products Dictyoceratin-A and -C as Selective Growth Inhibitors in Cancer Cells Adapted to Hypoxic Environments |
title | Target Identification of the Marine Natural Products Dictyoceratin-A and -C as Selective Growth Inhibitors in Cancer Cells Adapted to Hypoxic Environments |
title_full | Target Identification of the Marine Natural Products Dictyoceratin-A and -C as Selective Growth Inhibitors in Cancer Cells Adapted to Hypoxic Environments |
title_fullStr | Target Identification of the Marine Natural Products Dictyoceratin-A and -C as Selective Growth Inhibitors in Cancer Cells Adapted to Hypoxic Environments |
title_full_unstemmed | Target Identification of the Marine Natural Products Dictyoceratin-A and -C as Selective Growth Inhibitors in Cancer Cells Adapted to Hypoxic Environments |
title_short | Target Identification of the Marine Natural Products Dictyoceratin-A and -C as Selective Growth Inhibitors in Cancer Cells Adapted to Hypoxic Environments |
title_sort | target identification of the marine natural products dictyoceratin-a and -c as selective growth inhibitors in cancer cells adapted to hypoxic environments |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471994/ https://www.ncbi.nlm.nih.gov/pubmed/30857246 http://dx.doi.org/10.3390/md17030163 |
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