Mar. Drugs 2019, 17(3), 163; https://doi.org/10.3390/md17030163
Target Identification of the Marine Natural Products Dictyoceratin-A and -C as Selective Growth Inhibitors in Cancer Cells Adapted to Hypoxic Environments
Takashi Kawachi 1, Shun Tanaka 1, Akinori Fukuda 1, Yuji Sumii 1,†
, Andi Setiawan 2, Naoyuki Kotoku 1,†, Motomasa Kobayashi 1 and Masayoshi Arai 1,*
, Andi Setiawan 2, Naoyuki Kotoku 1,†, Motomasa Kobayashi 1 and Masayoshi Arai 1,*
1
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan
2
Department of Chemistry, Faculty of Science, Lampung University, J1. Prof. Dr. Sumantri Brodjonegoro No. 1, Bandar Lampung 35145, Indonesia
*
Author to whom correspondence should be addressed.
†
Current affiliations of Y.S. and N.K.: Graduate School of Engineering, Nagoya Institute of Technology, Nagoya 466-8555, Japan and School of Pharmaceutical Sciences, Ritsumeikan University, Shiga 525-8577, Japan respectively.
Received: 11 February 2019 / Revised: 1 March 2019 / Accepted: 4 March 2019 / Published: 8 March 2019
Abstract
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. View Full-TextKeywords:
dictyoceratin-A; hypoxia; cancer; RNA polymerase II-associated protein 3; probe molecule; target molecule
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Kawachi, T.; Tanaka, S.; Fukuda, A.; Sumii, Y.; Setiawan, A.; Kotoku, N.; Kobayashi, M.; Arai, M. Target Identification of the Marine Natural Products Dictyoceratin-A and -C as Selective Growth Inhibitors in Cancer Cells Adapted to Hypoxic Environments. Mar. Drugs 2019, 17, 163.
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