Target Identification of the Marine Natural Products Dictyoceratin-A and -C as Selective Growth Inhibitors in Cancer Cells Adapted to Hypoxic Environments.
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| 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.
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| Authors | Takashi Kawachi, Shun Tanaka, Akinori Fukuda, Yuji Sumii, Andi Setiawan, Naoyuki Kotoku, Motomasa Kobayashi, Masayoshi Arai |
| Journal | Marine drugs (Mar Drugs) Vol. 17 Issue 3 (Mar 08 2019) ISSN: 1660-3397 [Electronic] Switzerland |
| PMID | 30857246 (Publication Type: Journal Article) |
| Chemical References |
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