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Selective cytotoxicity of marine-derived fungal metabolite (3S,6S)-3,6-dibenzylpiperazine-2,5-dione against cancer cells adapted to nutrient starvation

The Journal of Antibiotics volume 73, pages 873–875 (2020)Cite this article

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Abstract

The cancer cells that are adapted to the hypoxic and nutrient-starved conditions of the tumor microenvironment have become a key target for anticancer therapies. In the course of search for selective cytotoxic substances against cancer cells adapted to nutrient starvation, (3S,6S)-3,6-dibenzylpiperazine-2,5-dione (1) was isolated from culture extract of marine-derived Paecilomyces formous 17D47-2. Compound 1 showed cytotoxic activity on the human pancreatic carcinoma PANC-1 cells adapted to glucose-starved conditions with IC50 value of 28 µM, whereas no effect was observed against PANC-1 cells under general culture conditions up to 1000 µM. Further studies on the mechanism of the selective cytotoxicity of 1 against the glucose-starved PANC-1 cells suggest that it may function via uncoupling of mitochondrial oxidative phosphorylation.

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Acknowledgements

The human pancreatic carcinoma cell line, PANC-1 (RCB2095), was provided by the RIKEN BRC through the National BioResource Project of the MEXT, Japan. We are indebted to Mr. Jianyu Lin and Mr. Waleed Abdellah Abdelnaime Mahmoud for their technical assistance. This research was funded by the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research [BINDS]) from the Japan Agency for Medical Research and Development (AMED) (grant no. JP20am0101084), the Kobayashi International Scholarship Foundation, and a Grant-in-Aid for Scientific Research B (grant nos. 18H02096 and 17H04645) from the Japan Society for the Promotion of Science (JSPS) to MA.

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  1. Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka 1-6, Suita, Osaka, 565-0871, Japan

    Rui Tang, Dongyi Zhou, Atsushi Kimishima & Masayoshi Arai

  2. Department of Chemistry, Faculty of Science, Lampung University, Jl. Prof. Dr. Sumantri Brodjonegoro No. 1, Bandar Lampung, 35145, Indonesia

    Andi Setiawan

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  1. Rui Tang
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Correspondence to Masayoshi Arai.

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Tang, R., Zhou, D., Kimishima, A. et al. Selective cytotoxicity of marine-derived fungal metabolite (3S,6S)-3,6-dibenzylpiperazine-2,5-dione against cancer cells adapted to nutrient starvation. J Antibiot 73, 873–875 (2020). https://doi.org/10.1038/s41429-020-0340-3

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