p53-dependent anti-proliferative and pro-apoptotic effects of a gold(I) N-heterocyclic carbene (NHC) complex in colorectal cancer cells

• Verfasst von: Dabiri, Yasamin [VerfasserIn]
• Verfasst von: Abu El Maaty, Mohamed A. [VerfasserIn]
• Verfasst von: Wölfl, Stefan [VerfasserIn]
• Verfasst von: Cheng, Xinlai [VerfasserIn]
• Titel: p53-dependent anti-proliferative and pro-apoptotic effects of a gold(I) N-heterocyclic carbene (NHC) complex in colorectal cancer cells
• Verf.angabe: Yasamin Dabiri, Mohamed A. Abu el Maaty, Hoi Yin Chan, Jessica Wölker, Ingo Ott, Stefan Wölfl, Xinlai Cheng
• E-Jahr: 2019
• Jahr: 29 May 2019
• Umfang: 16 S.
• Fussnoten: Gesehen am 02.07.2019
• Titel Quelle: Enthalten in: Frontiers in oncology
• Ort Quelle: Lausanne : Frontiers Media, 2011
• Jahr Quelle: 2019
• Band/Heft Quelle: 9(2019), Artikel-ID 438
• ISSN Quelle: 2234-943X
• DOI: doi:10.3389/fonc.2019.00438
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Apoptosis
• Sach-SW: Colorecta cancer
• Sach-SW: Gold(I) N-heterocyclic carbene complex
• Sach-SW: p21
• Sach-SW: p53
• Sach-SW: p73
• K10plus-PPN: 1668302624
• K10plus-PPN:
  Universitätsbibliothek
• Lokale URL UB: Zum Volltext

Abstract

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.