Caffeic Acid Phenethyl Ester (CAPE), a natural polyphenol to increase the therapeutic window for lung adenocarcinomas.

Autor: Prades-Sagarra E; The M-Lab, Department of Precision Medicine, GROW - School for Oncology and Reproduction, Maastricht University, 6229 ER Maastricht, The Netherlands., Laarakker F; The M-Lab, Department of Precision Medicine, GROW - School for Oncology and Reproduction, Maastricht University, 6229 ER Maastricht, The Netherlands., Dissy J; The M-Lab, Department of Precision Medicine, GROW - School for Oncology and Reproduction, Maastricht University, 6229 ER Maastricht, The Netherlands., Lieuwes NG; The M-Lab, Department of Precision Medicine, GROW - School for Oncology and Reproduction, Maastricht University, 6229 ER Maastricht, The Netherlands., Biemans R; The M-Lab, Department of Precision Medicine, GROW - School for Oncology and Reproduction, Maastricht University, 6229 ER Maastricht, The Netherlands., Dubail M; Institut Curie, Inserm U1021-CNRS UMR 3347, University Paris-Saclay, PSL University, Centre Universitaire, 91405 Orsay Cedex, France., Fouillade C; Institut Curie, Inserm U1021-CNRS UMR 3347, University Paris-Saclay, PSL University, Centre Universitaire, 91405 Orsay Cedex, France., Yaromina A; The M-Lab, Department of Precision Medicine, GROW - School for Oncology and Reproduction, Maastricht University, 6229 ER Maastricht, The Netherlands., Dubois LJ; The M-Lab, Department of Precision Medicine, GROW - School for Oncology and Reproduction, Maastricht University, 6229 ER Maastricht, The Netherlands. Electronic address: ludwig.dubois@maastrichtuniversity.nl.
Jazyk: angličtina
Zdroj: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology [Radiother Oncol] 2024 Jan; Vol. 190, pp. 110021. Date of Electronic Publication: 2023 Nov 22.
DOI: 10.1016/j.radonc.2023.110021
Abstrakt: Background and Purpose: Lung cancers are highly resistant to radiotherapy, necessitating the use of high doses, which leads to radiation toxicities such as radiation pneumonitis and fibrosis. Caffeic Acid Phenethyl Ester (CAPE) has been suggested to have anti-proliferative and pro-apoptotic effects in tumour cells, while radioprotective anti-inflammatory and anti-oxidant effects in the normal tissue. We investigated the radiosensitizing and radioprotective effects of CAPE in lung cancer cell lines and normal tissue in vitro and ex vivo, respectively.
Materials and Methods: The cytotoxic and radiosensitizing effects of CAPE in lung cancer were investigated using viability and clonogenic survival assays. The radioprotective effects of CAPE were assessed in vitro and ex vivo using precision cut lung slices (PCLS). Potential underlying molecular mechanisms of CAPE focusing on cell cycle, cell metabolism, mitochondrial function and pro-inflammatory markers were investigated.
Results: Treatment with CAPE decreased cell viability in a dose-dependent manner (IC 50 57.6 ± 16.6 μM). Clonogenic survival assays showed significant radiosensitization by CAPE in lung adenocarcinoma lines (p < 0.05), while no differences were found in non-adenocarcinoma lines (p ≥ 0.13). Cell cycle analysis showed an increased S-phase (p < 0.05) after incubation with CAPE in the majority of cell lines. Metabolic profiling showed that CAPE shifted cellular respiration towards glycolysis (p < 0.01), together with mitochondrial membrane depolarization (p < 0.01). CAPE induced a decrease in NF-κB activity in adenocarcinomas and decreased pro-inflammatory gene expression in PCLS.
Conclusion: The combination of CAPE and radiotherapy may be a potentially effective approach to increase the therapeutic window in lung cancer patients.
Competing Interests: Declaration of competing interest L.J.D. has, outside of the submitted work, shares in the companies Convert Pharmaceuticals and LivingMed Biotech, he is co-inventor of a non-issue, non-licensed patent on LSRT (N2024889). The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: