Two palladium (II) complexes derived from halogen-substituted Schiff bases and 2-picolylamine induce parthanatos-type cell death in sensitive and multi-drug resistant CCRF-CEM leukemia cells

Publication type:
Journal article
Metadata:
Autoren
  • Min Zhou
  • Joelle C Boulos
  • Ejlal A Omer
  • Hadi Amiri Rudbari
  • Tanja Schirmeister
  • Nicola Micale
  • Thomas Efferth
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:001059116300001&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1016/j.ejphar.2023.175980
eISSN
1879-0712
Externe Identifier
  • Clarivate Analytics Document Solution ID: Q7EL3
  • PubMed Identifier: 37567459
ISSN
0014-2999
Zeitschrift
EUROPEAN JOURNAL OF PHARMACOLOGY
Schlüsselwörter
  • Cell death
  • Drug design
  • Leukemia
  • Metallodrugs
  • Palladium -based complex
  • Parthanatos
Artikelnummer
ARTN 175980
Datum der Veröffentlichung
2023
Status
Published
Titel
Two palladium (II) complexes derived from halogen-substituted Schiff bases and 2-picolylamine induce parthanatos-type cell death in sensitive and multi-drug resistant CCRF-CEM leukemia cells
Sub types
  • Article
Ausgabe der Zeitschrift
956

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Min Zhou
  • Joelle C Boulos
  • Ejlal A Omer
  • Hadi Amiri Rudbari
  • Tanja Schirmeister
  • Nicola Micale
  • Thomas Efferth
DOI
10.1016/j.ejphar.2023.175980
ISSN
0014-2999
Zeitschrift
European Journal of Pharmacology
Sprache
en
Artikelnummer
175980
Paginierung
175980 - 175980
Datum der Veröffentlichung
2023
Status
Published
Herausgeber
Elsevier BV
Herausgeber URL
http://dx.doi.org/10.1016/j.ejphar.2023.175980
Datum der Datenerfassung
2023
Titel
Two palladium (II) complexes derived from halogen-substituted Schiff bases and 2-picolylamine induce parthanatos-type cell death in sensitive and multi-drug resistant CCRF-CEM leukemia cells
Ausgabe der Zeitschrift
956

Data source: Crossref

Abstract
The use of cisplatin and its derivatives in cancer treatment triggered the interest in metal-containing complexes as potential novel anticancer agents. Palladium (II)-based complexes have been synthesized in recent years with promising antitumor activity. Previously, we described the synthesis and cytotoxicity of palladium (II) complexes containing halogen-substituted Schiff bases and 2-picolylamine. Here, we selected two palladium (II) complexes with double chlorine-substitution or double iodine-substitution that displayed the best cytotoxicity in drug-sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cells for further biological investigation. Surprisingly, these compounds did not significantly induce apoptotic cell death. This study aims to reveal the major mode of cell death of these two palladium (II) complexes. We performed annexin V-FITC/PI staining and flow cytometric mitochondrial membrane potential measurement followed by western blotting, immunofluorescence microscopy, and alkaline single cell electrophoresis (comet assay). J4 and J6 still induced neither apoptosis nor necrosis in both leukemia cell lines. They also insufficiently induced autophagy as evidenced by Beclin and p62 detection in western blotting. Interestingly, J4 and J6 induced a novel mode of cell death (parthanatos) as mainly demonstrated in CCRF-CEM cells by hyper-activation of poly(ADP-ribose) polymerase 1 (PARP) and poly(ADP-ribose) (PAR) using western blotting, flow cytometric measurement of mitochondrial membrane potential collapse, nuclear translocation of apoptosis-inducing factor (AIF) by immunofluorescence microscopy, and DNA damage by alkaline single cell electrophoresis (comet assay). AIF translocation was also observed in CEM/ADR5000 cells. Thus, parthanatos was the predominant mode of cell death induced by J4 and J6, which explains the high cytotoxicity in CCRF-CEM and CEM/ADR5000 cells. J4 and J6 may be interesting drug candidates and deserve further investigations to overcome resistance of tumors against apoptosis. This study will promote the design of further novel palladium (II)-based complexes as chemotherapeutic agents.
Addresses
  • Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University-Mainz, Staudinger Weg 5, 55128, Mainz, Germany.
Autoren
  • Min Zhou
  • Joelle C Boulos
  • Ejlal A Omer
  • Hadi Amiri Rudbari
  • Tanja Schirmeister
  • Nicola Micale
  • Thomas Efferth
DOI
10.1016/j.ejphar.2023.175980
eISSN
1879-0712
Externe Identifier
  • PubMed Identifier: 37567459
Open access
false
ISSN
0014-2999
Zeitschrift
European journal of pharmacology
Schlüsselwörter
  • Cell Line, Tumor
  • Humans
  • Leukemia
  • Halogens
  • Palladium
  • Schiff Bases
  • Antineoplastic Agents, Phytogenic
  • Drug Resistance, Multiple
  • Cell Death
  • Apoptosis
  • Drug Resistance, Neoplasm
  • Parthanatos
Sprache
eng
Medium
Print-Electronic
Online publication date
2023
Paginierung
175980
Datum der Veröffentlichung
2023
Status
Published
Datum der Datenerfassung
2023
Titel
Two palladium (II) complexes derived from halogen-substituted Schiff bases and 2-picolylamine induce parthanatos-type cell death in sensitive and multi-drug resistant CCRF-CEM leukemia cells.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
956

Data source: Europe PubMed Central

Abstract
The use of cisplatin and its derivatives in cancer treatment triggered the interest in metal-containing complexes as potential novel anticancer agents. Palladium (II)-based complexes have been synthesized in recent years with promising antitumor activity. Previously, we described the synthesis and cytotoxicity of palladium (II) complexes containing halogen-substituted Schiff bases and 2-picolylamine. Here, we selected two palladium (II) complexes with double chlorine-substitution or double iodine-substitution that displayed the best cytotoxicity in drug-sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cells for further biological investigation. Surprisingly, these compounds did not significantly induce apoptotic cell death. This study aims to reveal the major mode of cell death of these two palladium (II) complexes. We performed annexin V-FITC/PI staining and flow cytometric mitochondrial membrane potential measurement followed by western blotting, immunofluorescence microscopy, and alkaline single cell electrophoresis (comet assay). J4 and J6 still induced neither apoptosis nor necrosis in both leukemia cell lines. They also insufficiently induced autophagy as evidenced by Beclin and p62 detection in western blotting. Interestingly, J4 and J6 induced a novel mode of cell death (parthanatos) as mainly demonstrated in CCRF-CEM cells by hyper-activation of poly(ADP-ribose) polymerase 1 (PARP) and poly(ADP-ribose) (PAR) using western blotting, flow cytometric measurement of mitochondrial membrane potential collapse, nuclear translocation of apoptosis-inducing factor (AIF) by immunofluorescence microscopy, and DNA damage by alkaline single cell electrophoresis (comet assay). AIF translocation was also observed in CEM/ADR5000 cells. Thus, parthanatos was the predominant mode of cell death induced by J4 and J6, which explains the high cytotoxicity in CCRF-CEM and CEM/ADR5000 cells. J4 and J6 may be interesting drug candidates and deserve further investigations to overcome resistance of tumors against apoptosis. This study will promote the design of further novel palladium (II)-based complexes as chemotherapeutic agents.
Date of acceptance
2023
Autoren
  • Min Zhou
  • Joelle C Boulos
  • Ejlal A Omer
  • Hadi Amiri Rudbari
  • Tanja Schirmeister
  • Nicola Micale
  • Thomas Efferth
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/37567459
DOI
10.1016/j.ejphar.2023.175980
eISSN
1879-0712
Zeitschrift
Eur J Pharmacol
Schlüsselwörter
  • Cell death
  • Drug design
  • Leukemia
  • Metallodrugs
  • Palladium-based complex
  • Parthanatos
  • Humans
  • Palladium
  • Halogens
  • Parthanatos
  • Schiff Bases
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm
  • Drug Resistance, Multiple
  • Antineoplastic Agents, Phytogenic
  • Cell Death
  • Apoptosis
  • Leukemia
Sprache
eng
Country
Netherlands
Paginierung
175980
PII
S0014-2999(23)00492-2
Datum der Veröffentlichung
2023
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2023
Titel
Two palladium (II) complexes derived from halogen-substituted Schiff bases and 2-picolylamine induce parthanatos-type cell death in sensitive and multi-drug resistant CCRF-CEM leukemia cells.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
956

Data source: PubMed

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