Therapeutic effects of Argyrin F in pancreatic adenocarcinoma

authored by

Xi Chen, Khac Cuong Bui, Samarpita Barat, Mai Ly Thi Nguyen, Przemyslaw Bozko, Bence Sipos, Markus Kalesse, Nisar P. Malek, Ruben R. Plentz

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with limited treatment options. The proteasome inhibitor Argyrin A, a cyclic peptide derived from the myxobacterium Archangium gephyra, shows antitumoral activities. We hypothesize that his analogue Argyrin F (AF) may also prevent PDAC progression. We have used PDAC cells and engineered mice (Pdx1-Cre; LSL-KrasG12D; p53 ^lox/+) to assess AF anticancer activity. We analyzed the effect of AF on proliferation and epithelial plasticity using MTT-, wound healing-, invasion-, colony formation-, apoptosis-, cell cycle- and senescence assays. In vivo treatment with AF, Gemcitabine (G) and combinational treatment (AF + G) was performed for survival analysis. AF inhibited cell proliferation, migration, invasion and colony formation in vitro. AF impaired epithelial-mesenchymal transition (EMT), caused considerable apoptosis and senescence in a dose- and time-dependent manner and affected cell cycle G₁/S phase transition. G treatment achieved longest mice survival, followed by AF + G and AF compared to vehicle group. However, AF + G treatment induced the largest reduction in tumor spread and ascites. In conclusion, we have demonstrated that AF prevents PDAC progression and that combined therapy was superior to AF monotherapy. Therefore, AF treatment might be useful as an additional therapy for PDAC.

Organisation(s)

Institute of Organic Chemistry

External Organisation(s)

University of Tübingen

Type

Article

Journal

Cancer letters

Volume

399

Pages

20-28

No. of pages

9

ISSN

0304-3835

Publication date

28.07.2017

Publication status

Published

Peer reviewed

Yes

ASJC Scopus subject areas

Oncology, Cancer Research

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Electronic version(s)

https://doi.org/10.1016/j.canlet.2017.04.003 (Access: Closed)