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p53-Dependent Anti-Proliferative and Pro-Apoptotic Effects of a Gold(I) N-Heterocyclic Carbene (NHC) Complex in Colorectal Cancer Cells
The tumor suppressor p53 has a diverse mutational profile in human malignancies, which is known to influence the potency of various chemotherapeutics, such as platins and anti-metabolites. However, the impact of the mutations in the TP53 gene (coding for p53) on the anti-cancer efficacy of gold comp...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2019
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558413/ https://www.ncbi.nlm.nih.gov/pubmed/31231607 http://dx.doi.org/10.3389/fonc.2019.00438 |
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author | Dabiri, Yasamin Abu el Maaty, Mohamed A. Chan, Hoi Yin Wölker, Jessica Ott, Ingo Wölfl, Stefan Cheng, Xinlai |
author_facet | Dabiri, Yasamin Abu el Maaty, Mohamed A. Chan, Hoi Yin Wölker, Jessica Ott, Ingo Wölfl, Stefan Cheng, Xinlai |
author_sort | Dabiri, Yasamin |
collection | PubMed |
description | The tumor suppressor p53 has a diverse mutational profile in human malignancies, which is known to influence the potency of various chemotherapeutics, such as platins and anti-metabolites. However, the impact of the mutations in the TP53 gene (coding for p53) on the anti-cancer efficacy of gold complexes remains incompletely understood. We therefore investigated the anti-tumor properties of a gold(I) N-heterocyclic carbene (NHC) complex–termed MC3–in human colorectal cancer (CRC) cell lines encompassing three different p53 variations: HCT116 wild-type (WT), HCT116 p53(−/−), and HT-29 (mutant; R273H). MC3 treatment induced intracellular reactive oxygen species (ROS) levels, and p21 expression, leading to cell cycle arrest in all cell lines, regardless of their p53 status. The pro-apoptotic response, however, was found to occur in a p53-dependent manner, with WT p53 harboring cells showing the highest responsiveness. Additionally, p73, which was speculated to substitute p53 in p53-deficient cells, was found to be markedly reduced with MC3 treatment in all the cell lines and knocking down its levels did not impact MC3's anti-tumor effects in HCT116 p53(−/−) cells. Collectively, our results suggest that this small molecule has anti-cancer properties in the context of deficient or mutant p53 and may therefore have chemotherapeutic potential for clinical application. |
format | Online Article Text |
id | pubmed-6558413 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-65584132019-06-21 p53-Dependent Anti-Proliferative and Pro-Apoptotic Effects of a Gold(I) N-Heterocyclic Carbene (NHC) Complex in Colorectal Cancer Cells Dabiri, Yasamin Abu el Maaty, Mohamed A. Chan, Hoi Yin Wölker, Jessica Ott, Ingo Wölfl, Stefan Cheng, Xinlai Front Oncol Oncology The tumor suppressor p53 has a diverse mutational profile in human malignancies, which is known to influence the potency of various chemotherapeutics, such as platins and anti-metabolites. However, the impact of the mutations in the TP53 gene (coding for p53) on the anti-cancer efficacy of gold complexes remains incompletely understood. We therefore investigated the anti-tumor properties of a gold(I) N-heterocyclic carbene (NHC) complex–termed MC3–in human colorectal cancer (CRC) cell lines encompassing three different p53 variations: HCT116 wild-type (WT), HCT116 p53(−/−), and HT-29 (mutant; R273H). MC3 treatment induced intracellular reactive oxygen species (ROS) levels, and p21 expression, leading to cell cycle arrest in all cell lines, regardless of their p53 status. The pro-apoptotic response, however, was found to occur in a p53-dependent manner, with WT p53 harboring cells showing the highest responsiveness. Additionally, p73, which was speculated to substitute p53 in p53-deficient cells, was found to be markedly reduced with MC3 treatment in all the cell lines and knocking down its levels did not impact MC3's anti-tumor effects in HCT116 p53(−/−) cells. Collectively, our results suggest that this small molecule has anti-cancer properties in the context of deficient or mutant p53 and may therefore have chemotherapeutic potential for clinical application. Frontiers Media S.A. 2019-05-29 /pmc/articles/PMC6558413/ /pubmed/31231607 http://dx.doi.org/10.3389/fonc.2019.00438 Text en Copyright © 2019 Dabiri, Abu el Maaty, Chan, Wölker, Ott, Wölfl and Cheng. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Dabiri, Yasamin Abu el Maaty, Mohamed A. Chan, Hoi Yin Wölker, Jessica Ott, Ingo Wölfl, Stefan Cheng, Xinlai p53-Dependent Anti-Proliferative and Pro-Apoptotic Effects of a Gold(I) N-Heterocyclic Carbene (NHC) Complex in Colorectal Cancer Cells |
title | p53-Dependent Anti-Proliferative and Pro-Apoptotic Effects of a Gold(I) N-Heterocyclic Carbene (NHC) Complex in Colorectal Cancer Cells |
title_full | p53-Dependent Anti-Proliferative and Pro-Apoptotic Effects of a Gold(I) N-Heterocyclic Carbene (NHC) Complex in Colorectal Cancer Cells |
title_fullStr | p53-Dependent Anti-Proliferative and Pro-Apoptotic Effects of a Gold(I) N-Heterocyclic Carbene (NHC) Complex in Colorectal Cancer Cells |
title_full_unstemmed | p53-Dependent Anti-Proliferative and Pro-Apoptotic Effects of a Gold(I) N-Heterocyclic Carbene (NHC) Complex in Colorectal Cancer Cells |
title_short | p53-Dependent Anti-Proliferative and Pro-Apoptotic Effects of a Gold(I) N-Heterocyclic Carbene (NHC) Complex in Colorectal Cancer Cells |
title_sort | p53-dependent anti-proliferative and pro-apoptotic effects of a gold(i) n-heterocyclic carbene (nhc) complex in colorectal cancer cells |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558413/ https://www.ncbi.nlm.nih.gov/pubmed/31231607 http://dx.doi.org/10.3389/fonc.2019.00438 |
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