Novel gold(I) complexes induce apoptosis in leukemia cells via the ROS-induced mitochondrial pathway with an upregulation of Harakiri and overcome multi drug resistances in leukemia and lymphoma cells and sensitize drug resistant tumor cells to apoptosis in vitro
Gold complexes could be promising for tumor therapy because of their cytotoxic and cytostatic properties. We present novel gold(I) complexes and clarify whether they also show antitumor activity by studying apoptosis induction in different tumor cell lines in vitro, comparing the compounds on resist...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2023-05-01
|
Series: | Biomedicine & Pharmacotherapy |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223002950 |
_version_ | 1797857688161353728 |
---|---|
author | Marie-C. Ahrweiler-Sawaryn Animesh Biswas Corazon Frias Jerico Frias Nicola L. Wilke Nathalie Wilke Albrecht Berkessel Aram Prokop |
author_facet | Marie-C. Ahrweiler-Sawaryn Animesh Biswas Corazon Frias Jerico Frias Nicola L. Wilke Nathalie Wilke Albrecht Berkessel Aram Prokop |
author_sort | Marie-C. Ahrweiler-Sawaryn |
collection | DOAJ |
description | Gold complexes could be promising for tumor therapy because of their cytotoxic and cytostatic properties. We present novel gold(I) complexes and clarify whether they also show antitumor activity by studying apoptosis induction in different tumor cell lines in vitro, comparing the compounds on resistant cells and analyzing the mechanism of action. We particularly highlight one gold complex that shows cytostatic and cytotoxic effects on leukemia and lymphoma cells already in the nanomolar range, induces apoptosis via the intrinsic signaling pathway, and plays a role in the production of reactive oxygen species. Furthermore, not only did we demonstrate a large number of resistance overcomes on resistant cell lines, but some of these cell lines were significantly more sensitive to the new gold compound. Our results show promising properties for the gold compound as anti-tumor drug and suggest that it can subvert resistance mechanisms and thus targets resistant cells for killing. |
first_indexed | 2024-04-09T21:00:51Z |
format | Article |
id | doaj.art-725cc077cfbe49f69f52e4a6bff9cc37 |
institution | Directory Open Access Journal |
issn | 0753-3322 |
language | English |
last_indexed | 2024-04-09T21:00:51Z |
publishDate | 2023-05-01 |
publisher | Elsevier |
record_format | Article |
series | Biomedicine & Pharmacotherapy |
spelling | doaj.art-725cc077cfbe49f69f52e4a6bff9cc372023-03-29T09:23:26ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-05-01161114507Novel gold(I) complexes induce apoptosis in leukemia cells via the ROS-induced mitochondrial pathway with an upregulation of Harakiri and overcome multi drug resistances in leukemia and lymphoma cells and sensitize drug resistant tumor cells to apoptosis in vitroMarie-C. Ahrweiler-Sawaryn0Animesh Biswas1Corazon Frias2Jerico Frias3Nicola L. Wilke4Nathalie Wilke5Albrecht Berkessel6Aram Prokop7Department of Pediatric Hematology/Oncology, Helios Clinic Schwerin, Wismarsche Straße 393-397, 19055 Schwerin, Germany; Department of Pediatric Hematology/Oncology, Children’s Hospital Cologne, Amsterdamer Straße 59, 50735 Cologne, Germany; Corresponding author at: Department of Pediatric Hematology/Oncology, Helios Clinic Schwerin, Wismarsche Straße 393-397, 19055 Schwerin, Germany.Department of Chemistry, Organic Chemistry, University of Cologne, Greinstrasse 4, 50939 Cologne, GermanyDepartment of Pediatric Hematology/Oncology, Helios Clinic Schwerin, Wismarsche Straße 393-397, 19055 Schwerin, Germany; Department of Pediatric Hematology/Oncology, Children’s Hospital Cologne, Amsterdamer Straße 59, 50735 Cologne, GermanyDepartment of Pediatric Hematology/Oncology, Helios Clinic Schwerin, Wismarsche Straße 393-397, 19055 Schwerin, Germany; Department of Pediatric Hematology/Oncology, Children’s Hospital Cologne, Amsterdamer Straße 59, 50735 Cologne, GermanyDepartment of Pediatric Hematology/Oncology, Helios Clinic Schwerin, Wismarsche Straße 393-397, 19055 Schwerin, Germany; Department of Pediatric Hematology/Oncology, Children’s Hospital Cologne, Amsterdamer Straße 59, 50735 Cologne, GermanyDepartment of Pediatric Hematology/Oncology, Helios Clinic Schwerin, Wismarsche Straße 393-397, 19055 Schwerin, Germany; Department of Pediatric Hematology/Oncology, Children’s Hospital Cologne, Amsterdamer Straße 59, 50735 Cologne, GermanyDepartment of Chemistry, Organic Chemistry, University of Cologne, Greinstrasse 4, 50939 Cologne, GermanyDepartment of Pediatric Hematology/Oncology, Helios Clinic Schwerin, Wismarsche Straße 393-397, 19055 Schwerin, Germany; Department of Pediatric Hematology/Oncology, Children’s Hospital Cologne, Amsterdamer Straße 59, 50735 Cologne, Germany; Department of Research, Medical School Hamburg (MSH), University of Applied Sciences and Medical University, Am Kaiserkai 1, 20457, GermanyGold complexes could be promising for tumor therapy because of their cytotoxic and cytostatic properties. We present novel gold(I) complexes and clarify whether they also show antitumor activity by studying apoptosis induction in different tumor cell lines in vitro, comparing the compounds on resistant cells and analyzing the mechanism of action. We particularly highlight one gold complex that shows cytostatic and cytotoxic effects on leukemia and lymphoma cells already in the nanomolar range, induces apoptosis via the intrinsic signaling pathway, and plays a role in the production of reactive oxygen species. Furthermore, not only did we demonstrate a large number of resistance overcomes on resistant cell lines, but some of these cell lines were significantly more sensitive to the new gold compound. Our results show promising properties for the gold compound as anti-tumor drug and suggest that it can subvert resistance mechanisms and thus targets resistant cells for killing.http://www.sciencedirect.com/science/article/pii/S0753332223002950NHC-Au(I) complexesMitochondrial pathwayApoptosisROSBcl-2Harakiri |
spellingShingle | Marie-C. Ahrweiler-Sawaryn Animesh Biswas Corazon Frias Jerico Frias Nicola L. Wilke Nathalie Wilke Albrecht Berkessel Aram Prokop Novel gold(I) complexes induce apoptosis in leukemia cells via the ROS-induced mitochondrial pathway with an upregulation of Harakiri and overcome multi drug resistances in leukemia and lymphoma cells and sensitize drug resistant tumor cells to apoptosis in vitro Biomedicine & Pharmacotherapy NHC-Au(I) complexes Mitochondrial pathway Apoptosis ROS Bcl-2 Harakiri |
title | Novel gold(I) complexes induce apoptosis in leukemia cells via the ROS-induced mitochondrial pathway with an upregulation of Harakiri and overcome multi drug resistances in leukemia and lymphoma cells and sensitize drug resistant tumor cells to apoptosis in vitro |
title_full | Novel gold(I) complexes induce apoptosis in leukemia cells via the ROS-induced mitochondrial pathway with an upregulation of Harakiri and overcome multi drug resistances in leukemia and lymphoma cells and sensitize drug resistant tumor cells to apoptosis in vitro |
title_fullStr | Novel gold(I) complexes induce apoptosis in leukemia cells via the ROS-induced mitochondrial pathway with an upregulation of Harakiri and overcome multi drug resistances in leukemia and lymphoma cells and sensitize drug resistant tumor cells to apoptosis in vitro |
title_full_unstemmed | Novel gold(I) complexes induce apoptosis in leukemia cells via the ROS-induced mitochondrial pathway with an upregulation of Harakiri and overcome multi drug resistances in leukemia and lymphoma cells and sensitize drug resistant tumor cells to apoptosis in vitro |
title_short | Novel gold(I) complexes induce apoptosis in leukemia cells via the ROS-induced mitochondrial pathway with an upregulation of Harakiri and overcome multi drug resistances in leukemia and lymphoma cells and sensitize drug resistant tumor cells to apoptosis in vitro |
title_sort | novel gold i complexes induce apoptosis in leukemia cells via the ros induced mitochondrial pathway with an upregulation of harakiri and overcome multi drug resistances in leukemia and lymphoma cells and sensitize drug resistant tumor cells to apoptosis in vitro |
topic | NHC-Au(I) complexes Mitochondrial pathway Apoptosis ROS Bcl-2 Harakiri |
url | http://www.sciencedirect.com/science/article/pii/S0753332223002950 |
work_keys_str_mv | AT mariecahrweilersawaryn novelgoldicomplexesinduceapoptosisinleukemiacellsviatherosinducedmitochondrialpathwaywithanupregulationofharakiriandovercomemultidrugresistancesinleukemiaandlymphomacellsandsensitizedrugresistanttumorcellstoapoptosisinvitro AT animeshbiswas novelgoldicomplexesinduceapoptosisinleukemiacellsviatherosinducedmitochondrialpathwaywithanupregulationofharakiriandovercomemultidrugresistancesinleukemiaandlymphomacellsandsensitizedrugresistanttumorcellstoapoptosisinvitro AT corazonfrias novelgoldicomplexesinduceapoptosisinleukemiacellsviatherosinducedmitochondrialpathwaywithanupregulationofharakiriandovercomemultidrugresistancesinleukemiaandlymphomacellsandsensitizedrugresistanttumorcellstoapoptosisinvitro AT jericofrias novelgoldicomplexesinduceapoptosisinleukemiacellsviatherosinducedmitochondrialpathwaywithanupregulationofharakiriandovercomemultidrugresistancesinleukemiaandlymphomacellsandsensitizedrugresistanttumorcellstoapoptosisinvitro AT nicolalwilke novelgoldicomplexesinduceapoptosisinleukemiacellsviatherosinducedmitochondrialpathwaywithanupregulationofharakiriandovercomemultidrugresistancesinleukemiaandlymphomacellsandsensitizedrugresistanttumorcellstoapoptosisinvitro AT nathaliewilke novelgoldicomplexesinduceapoptosisinleukemiacellsviatherosinducedmitochondrialpathwaywithanupregulationofharakiriandovercomemultidrugresistancesinleukemiaandlymphomacellsandsensitizedrugresistanttumorcellstoapoptosisinvitro AT albrechtberkessel novelgoldicomplexesinduceapoptosisinleukemiacellsviatherosinducedmitochondrialpathwaywithanupregulationofharakiriandovercomemultidrugresistancesinleukemiaandlymphomacellsandsensitizedrugresistanttumorcellstoapoptosisinvitro AT aramprokop novelgoldicomplexesinduceapoptosisinleukemiacellsviatherosinducedmitochondrialpathwaywithanupregulationofharakiriandovercomemultidrugresistancesinleukemiaandlymphomacellsandsensitizedrugresistanttumorcellstoapoptosisinvitro |