Class IV Lasso Peptides Synergistically Induce Proliferation of Cancer Cells and Sensitize Them to Doxorubicin

iScience

Finn L. Aachmann¹  Yan-Ru Cao²  Tobias Busche²  Jörn Kalinowski²  Martin Zehl³  Madhurendra Singh⁴  Shiva Rezaei⁴  Sergey B. Zotchev⁴  Christian Rückert⁵  Jaime Felipe Guerrero-Garzón⁶  Eva Madland⁷  Ernst Urban⁷  Gaston Courtade⁷  Cheng-lin Jiang⁸  Galina Selivanova⁸  Yi Jiang⁸ 

[1] Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran;Center for Biotechnology, Bielefeld University, Universitätsstraße 27, 33615 Bielefeld, Germany;Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna 1090, Austria;Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 17165 Stockholm, Sweden;Department of Pharmaceutical Chemistry, University of Vienna, Vienna 1090, Austria;Department of Pharmacognosy, University of Vienna, Vienna 1090, Austria;NOBIPOL, Department of Biotechnology and Food Science, NTNU Norwegian University of Science and Technology, 7034 Trondheim, Norway;Yunnan Institute of Microbiology, Yunnan University, 650091 Kunming, P.R.China;

关键词: Biological Sciences;    Biochemistry;    Microbiology;    Biotechnology;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: Heterologous expression of a biosynthesis gene cluster from Amycolatopsis sp. resulted in the discovery of two unique class IV lasso peptides, felipeptins A1 and A2. A mixture of felipeptins stimulated proliferation of cancer cells, while having no such effect on the normal cells. Detailed investigation revealed, that pre-treatment of cancer cells with a mixture of felipeptins resulted in downregulation of the tumor suppressor Rb, making the cancer cells to proliferate faster. Pre-treatment with felipeptins made cancer cells considerably more sensitive to the anticancer agent doxorubicin and re-sensitized doxorubicin-resistant cells to this drug. Structural characterization and binding experiments showed an interaction between felipeptins resulting in complex formation, which explains their synergistic effect. This discovery may open an alternative avenue in cancer treatment, helping to eliminate quiescent cells that often lead to cancer relapse.

【 授权许可】

Unknown