Oncotarget

Research Papers:

The phytohormone forchlorfenuron decreases viability and proliferation of malignant mesothelioma cells in vitro and in vivo

Walter Blum, Thomas Henzi, László Pecze, Kim-Long Diep, Christian G. Bochet and Beat Schwaller

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Oncotarget. 2019; 10:6944-6956. https://doi.org/10.18632/oncotarget.27341

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Abstract

Walter Blum1, Thomas Henzi1, László Pecze1, Kim-Long Diep2, Christian G. Bochet2 and Beat Schwaller1

1 Section of Medicine, University of Fribourg, CH-1700 Fribourg, Switzerland

2 Department of Chemistry, University of Fribourg, CH-1700 Fribourg, Switzerland

Correspondence to:

Beat Schwaller,email: Beat.Schwaller@unifr.ch

Keywords: malignant mesothelioma; septin cytoskeleton; septin 7; forchlorfenuron; FCF

Received: July 10, 2019     Accepted: October 26, 2019     Published: December 10, 2019

ABSTRACT

Malignant mesothelioma (MM) is one of the most aggressive cancer types with a patient’s life expectancy of typically less than one year upon diagnosis. The urgency of finding novel therapeutic approaches to treat mesothelioma is evident. Here we tested the effect of the plant-growth regulator forchlorfenuron (FCF), an inhibitor of septin function(s) in mammalian cells, on the viability and proliferation of MM cell lines, as well as other tumor cell lines derived from lung, prostate, colon, ovary, cervix and breast. Exposure to FCF strongly inhibited proliferation of human and mouse (most efficiently epithelioid) MM cells and all other tumor cells in a concentration-dependent manner and led to cell cycle arrest and cell death. The role of septin 7 (SEPT7), a presumably essential target of FCF in MM cells was confirmed by an shRNA strategy. FCF was robustly inhibiting tumor cell growth in vitro at low micromolar (IC50: ≈20-60µM) concentrations and more promisingly also in vivo. Initial experiments with FCF analogous revealed the importance of FCF’s chloride group for efficient cell growth inhibition. FCF’s rather low systemic toxicity might warrant for an extended search for other related and possibly more potent FCF analogues to target MM and putatively other septin-dependent tumors.


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