PMID- 38000688
OWN - NLM
STAT- MEDLINE
DCOM- 20240220
LR  - 20240226
IS  - 1879-0887 (Electronic)
IS  - 0167-8140 (Linking)
VI  - 190
DP  - 2024 Jan
TI  - Caffeic Acid Phenethyl Ester (CAPE), a natural polyphenol to increase the 
      therapeutic window for lung adenocarcinomas.
PG  - 110021
LID - S0167-8140(23)09328-3 [pii]
LID - 10.1016/j.radonc.2023.110021 [doi]
AB  - 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 muM). 
      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-kappaB 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.
CI  - Copyright (c) 2023 The Author(s). Published by Elsevier B.V. All rights reserved.
FAU - Prades-Sagarra, E
AU  - Prades-Sagarra E
AD  - The M-Lab, Department of Precision Medicine, GROW - School for Oncology and 
      Reproduction, Maastricht University, 6229 ER Maastricht, The Netherlands.
FAU - Laarakker, F
AU  - Laarakker F
AD  - The M-Lab, Department of Precision Medicine, GROW - School for Oncology and 
      Reproduction, Maastricht University, 6229 ER Maastricht, The Netherlands.
FAU - Dissy, J
AU  - Dissy J
AD  - The M-Lab, Department of Precision Medicine, GROW - School for Oncology and 
      Reproduction, Maastricht University, 6229 ER Maastricht, The Netherlands.
FAU - Lieuwes, N G
AU  - Lieuwes NG
AD  - The M-Lab, Department of Precision Medicine, GROW - School for Oncology and 
      Reproduction, Maastricht University, 6229 ER Maastricht, The Netherlands.
FAU - Biemans, R
AU  - Biemans R
AD  - The M-Lab, Department of Precision Medicine, GROW - School for Oncology and 
      Reproduction, Maastricht University, 6229 ER Maastricht, The Netherlands.
FAU - Dubail, M
AU  - Dubail M
AD  - Institut Curie, Inserm U1021-CNRS UMR 3347, University Paris-Saclay, PSL 
      University, Centre Universitaire, 91405 Orsay Cedex, France.
FAU - Fouillade, C
AU  - Fouillade C
AD  - Institut Curie, Inserm U1021-CNRS UMR 3347, University Paris-Saclay, PSL 
      University, Centre Universitaire, 91405 Orsay Cedex, France.
FAU - Yaromina, A
AU  - Yaromina A
AD  - The M-Lab, Department of Precision Medicine, GROW - School for Oncology and 
      Reproduction, Maastricht University, 6229 ER Maastricht, The Netherlands.
FAU - Dubois, L J
AU  - Dubois LJ
AD  - 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.
LA  - eng
PT  - Journal Article
DEP - 20231122
PL  - Ireland
TA  - Radiother Oncol
JT  - Radiotherapy and oncology : journal of the European Society for Therapeutic 
      Radiology and Oncology
JID - 8407192
RN  - G960R9S5SK (caffeic acid phenethyl ester)
RN  - 0 (Polyphenols)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Caffeic Acids)
RN  - ML9LGA7468 (Phenylethyl Alcohol)
SB  - IM
MH  - Humans
MH  - Polyphenols
MH  - *Adenocarcinoma of Lung/radiotherapy
MH  - *Antineoplastic Agents/pharmacology
MH  - Caffeic Acids/pharmacology
MH  - *Lung Neoplasms/radiotherapy/pathology
MH  - *Adenocarcinoma/radiotherapy
MH  - Cell Line, Tumor
MH  - Phenylethyl Alcohol/*analogs & derivatives
OTO - NOTNLM
OT  - Caffeic Acid Phenethyl Ester
OT  - Lung cancer
OT  - Lung toxicity
OT  - Radiation-induced adverse effects
OT  - Radiosensitization
COIS- 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.
EDAT- 2023/11/25 07:42
MHDA- 2024/02/20 11:50
CRDT- 2023/11/24 19:29
PHST- 2023/06/13 00:00 [received]
PHST- 2023/10/16 00:00 [revised]
PHST- 2023/11/15 00:00 [accepted]
PHST- 2024/02/20 11:50 [medline]
PHST- 2023/11/25 07:42 [pubmed]
PHST- 2023/11/24 19:29 [entrez]
AID - S0167-8140(23)09328-3 [pii]
AID - 10.1016/j.radonc.2023.110021 [doi]
PST - ppublish
SO  - Radiother Oncol. 2024 Jan;190:110021. doi: 10.1016/j.radonc.2023.110021. Epub 
      2023 Nov 22.