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 compl...
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| Main Authors: | , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
29 May 2019
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| In: |
Frontiers in oncology
Year: 2019, Volume: 9 |
| ISSN: | 2234-943X |
| DOI: | 10.3389/fonc.2019.00438 |
| Online Access: | Verlag, Volltext: https://doi.org/10.3389/fonc.2019.00438 Verlag, Volltext: https://www.frontiersin.org/articles/10.3389/fonc.2019.00438/full 
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| Author Notes: | Yasamin Dabiri, Mohamed A. Abu el Maaty, Hoi Yin Chan, Jessica Wölker, Ingo Ott, Stefan Wölfl, Xinlai Cheng |
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| 520 | |a 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. | ||
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