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Journal of Natural Medicines

, Volume 71, Issue 1, pp 44–49 | Cite as

Marine spongean polybrominated diphenyl ethers, selective growth inhibitors against the cancer cells adapted to glucose starvation, inhibits mitochondrial complex II

  • Masayoshi Arai
  • Dayoung Shin
  • Kentaro Kamiya
  • Ryosuke Ishida
  • Andi Setiawan
  • Naoyuki Kotoku
  • Motomasa Kobayashi
Original Paper

Abstract

In the course of search for selective growth inhibitors against the cancer cells adapted to nutrient starvation, two polybrominated diphenyl ethers, 3,4,5-tribromo-2-(2′,4′-dibromophenoxy)-phenol (1) and 3,5-dibromo-2-(2′,4′-dibromophenoxy)-phenol (2) were isolated from an Indonesian marine sponge of Dysidea sp. Compounds 1 and 2 showed the anti-proliferative activity against PANC-1 cells under glucose-starved conditions with IC50 values of 2.1 and 3.8 µM, respectively, whereas no growth inhibition was observed up to 30 µM in the general culture conditions. The further mechanistic analysis indicated that compound 1 might act mainly by inhibiting complex II in the mitochondrial electron transport chain.

Keywords

Polybrominated diphenyl ether Marine sponge Cancer Glucose starvation Mitochondrial electron transport chain 

Notes

Acknowledgments

The human pancreatic carcinoma cell line, PANC-1 (RCB2095), was provided by the RIKEN BRC through the National Bio-Resource Project of the MEXT, Japan. The authors are grateful to Dr. Nicole J. de Voogd, National Museum of Natural History, the Netherlands for identifying the sponge specimen. This study was financially supported by the Platform Project for Supporting in Drug Discovery and Life Science Research (Platform for Drug Discovery, Informatics, and Structural Life Science) from the Japan Agency for Medical Research and development (AMED), the Grant-in-Aid for Scientific Research from Japan Society for the Promotion of Science (JSPS, 15H03114, 26242074, and 26305002), and the Grant-in-Aid for Scientific Research on Innovative Areas from MEXT (23102005).

Supplementary material

11418_2016_1025_MOESM1_ESM.docx (109 kb)
Fig. S1 Representative original image of western blotting analysis for Fig. 3b (DOCX 110 kb)

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Copyright information

© The Japanese Society of Pharmacognosy and Springer Japan 2016

Authors and Affiliations

  • Masayoshi Arai
    • 1
  • Dayoung Shin
    • 1
  • Kentaro Kamiya
    • 1
  • Ryosuke Ishida
    • 1
  • Andi Setiawan
    • 2
  • Naoyuki Kotoku
    • 1
  • Motomasa Kobayashi
    • 1
  1. 1.Graduate School of Pharmaceutical SciencesOsaka UniversitySuitaJapan
  2. 2.Department of Chemistry, Faculty of ScienceLampung UniversityBandar LampungIndonesia

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