Target Identification of the Marine Natural Products Dictyoceratin-A and -C as Selective Growth Inhibitors in Cancer Cells Adapted to Hypoxic Environments

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.

Mar. Drugs 2019, 17(3), 163; https://doi.org/10.3390/md17030163

Received: 11 February 2019 / Revised: 1 March 2019 / Accepted: 4 March 2019 / Published: 8 March 2019

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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. View Full-Text

Keywords: dictyoceratin-A; hypoxia; cancer; RNA polymerase II-associated protein 3; probe molecule; target molecule

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MDPI and ACS Style

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. https://doi.org/10.3390/md17030163

AMA Style

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. Marine Drugs. 2019; 17(3):163. https://doi.org/10.3390/md17030163

Chicago/Turabian Style

Kawachi, Takashi, Shun Tanaka, Akinori Fukuda, Yuji Sumii, Andi Setiawan, Naoyuki Kotoku, Motomasa Kobayashi, and Masayoshi Arai. 2019. "Target Identification of the Marine Natural Products Dictyoceratin-A and -C as Selective Growth Inhibitors in Cancer Cells Adapted to Hypoxic Environments" Marine Drugs 17, no. 3: 163. https://doi.org/10.3390/md17030163

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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

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