Universität zu Köln

Hopff, Sina M., Wang, Qifang, Frias, Corazon, Ahrweiler, Marie, Wilke, Nicola, Wilke, Nathalie, Berkessel, Albrecht and Prokop, Aram (2021). A metal-free salalen ligand with anti-tumor and synergistic activity in resistant leukemia and solid tumor cells via mitochondrial pathway. J. Cancer Res. Clin. Oncol., 147 (9). S. 2591 - 2608. NEW YORK: SPRINGER. ISSN 1432-1335

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Abstract

Purpose Since the discovery of the well-known cis-platin, transition metal complexes are highly recognized as cytostatic agents. However, toxic side effects of the metal ions present in the complexes may pose significant problems for their future development. Therefore, we investigated the metal-free salalen ligand WQF 044. Methods DNA fragmentations in leukemia (Nalm6) and solid tumor cells (BJAB, MelHO, MCF-7, RM82) proved the apoptotic effects of WQF 044, its overcoming of resistances and the cellular pathways that are affected by the substance. The apoptotic mechanisms finding were supported by western blot analysis, measurement of the mitochondrial membrane potential and polymerase chain reactions. Results A complex intervention in the mitochondrial pathway of apoptosis with a Bcl-2 and caspase dependence was observed. Additionally, a wide range of tumors were affected by the ligand in a low micromolar range in-vitro. The compound overcame multidrug resistances in P-gp over-expressed acute lymphoblastic leukemia and CD95-downregulated Ewing's sarcoma cells. Quite remarkable synergistic effects with vincristine were observed in Burkitt-like lymphoma cells. Conclusion The investigation of a metal-free salalen ligand as a potential anti-cancer drug revealed in promising results for a future clinical use.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hopff, Sina M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wang, Qifang UNSPECIFIED UNSPECIFIED UNSPECIFIED Frias, Corazon UNSPECIFIED UNSPECIFIED UNSPECIFIED Ahrweiler, Marie UNSPECIFIED UNSPECIFIED UNSPECIFIED Wilke, Nicola UNSPECIFIED UNSPECIFIED UNSPECIFIED Wilke, Nathalie UNSPECIFIED UNSPECIFIED UNSPECIFIED Berkessel, Albrecht UNSPECIFIED UNSPECIFIED UNSPECIFIED Prokop, Aram UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-577777
DOI:	10.1007/s00432-021-03679-3
Journal or Publication Title:	J. Cancer Res. Clin. Oncol.
Volume:	147
Number:	9
Page Range:	S. 2591 - 2608
Date:	2021
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-1335
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MULTIDRUG-RESISTANCE; MOLECULAR-MECHANISMS; INDUCED APOPTOSIS; DRUG RESISTANCE; P-GLYCOPROTEIN; EWING SARCOMA; COMPLEXES; CANCER; DEATH; BCL-2 Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/57777