1. Furospinosulin-1, Marine Spongean Furanosesterterpene, Suppresses the Growth of Hypoxia-Adapted Cancer Cells by Binding to Transcriptional Regulators p54nrband LEDGF/p75
- Author
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Haruhiko Kamada, Hiroko Endo, Naoyuki Kotoku, Takashi Kawachi, Yasuo Tsutsumi, Masayoshi Arai, Masahiro Inoue, Shin-ichi Tsunoda, Hiroki Sato, Motomasa Kobayashi, and Chiaki Nakata
- Subjects
0301 basic medicine ,Sesterterpenes ,Fluorescent Antibody Technique ,Biology ,Bioinformatics ,Biochemistry ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Nuclear Matrix-Associated Proteins ,In vivo ,Cancer stem cell ,Neoplasms ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Animals ,Humans ,Mode of action ,Molecular Biology ,Molecular Structure ,Binding protein ,Organic Chemistry ,RNA-Binding Proteins ,Cancer ,Hypoxia (medical) ,medicine.disease ,Cell Hypoxia ,Cell biology ,DNA-Binding Proteins ,030104 developmental biology ,chemistry ,Gene Knockdown Techniques ,Cancer cell ,Intercellular Signaling Peptides and Proteins ,Octamer Transcription Factors ,Molecular Medicine ,Cisplatin ,Growth inhibition ,medicine.symptom ,Protein Binding - Abstract
Hypoxia-adapted cancer cells in tumors contribute to the pathological progression of cancer. Cancer research has therefore focused on the identification of molecules responsible for hypoxia adaptation in cancer cells, as well as the development of new compounds with action against hypoxia-adapted cancer cells. The marine natural product furospinosulin-1 (1) has displayed hypoxia-selective growth inhibition against cultured cancer cells, and has shown in vivo anti-tumor activity, although its precise mode of action and molecular targets remain unclear. In this study, we found that 1 is selectively effective against hypoxic regions of tumors, and that it directly binds to the transcriptional regulators p54(nrb) and LEDGF/p75, which have not been previously identified as mediators of hypoxia adaptation in cancer cells.
- Published
- 2015
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