Abstract
Prostate stroma can regulate the growth and metastasis of prostate cancer through the tumor–stromal cell interactions. Thus, small molecules that modulate the tumor–stromal cell interactions will have a chance to become new antitumor drugs. In the course of our screening of the modulators, we isolated three new natural compounds, NBRI16716A (1), NBRI16716B (2) and NBRI16716C (3), from the fermentation broth of Perisporiopsis melioloides Mer-f16716, although compound 2 was already reported as a chemical degradation product of isotriornicin. Compounds 1 and 2 inhibited the growth of human prostate cancer DU-145 cells in the coculture with human prostate stromal cells (PrSCs) more strongly than that of DU-145 cells alone. Furthermore, both compounds showed antitumor effect against xenograft models of DU-145 cells and PrSCs in vivo.
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Acknowledgements
We are grateful to Dr K Isshiki and Dr N Sakata (Mercian Corporation Bioresource Laboratories) for their valuable discussions. We also thank Dr R Sawa and Ms Y Kubota (Microbial Chemistry Research Center) for analysis of HRESI-MS and NMR measurements, and Ms K Adachi and Ms E Satoh for their technical assistance. This work was supported in part by a grant-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
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Kawada, M., Someno, T., Inoue, H. et al. NBRI16716A, a new antitumor compound against human prostate cancer cells, produced by Perisporiopsis melioloides Mer-f16716. J Antibiot 63, 319–323 (2010). https://doi.org/10.1038/ja.2010.42
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DOI: https://doi.org/10.1038/ja.2010.42
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