Universität zu Köln

Abodo Onambele, Liliane, Hoffmann, Natalie, Kater, Lisa, Hemmersbach, Lars, Neudorfl, Jorg-Martin, Sitnikov, Nikolay, Kater, Benjamin, Frias, Corazon, Schmalz, Hans-Gunther and Prokop, Aram (2022). An organometallic analogue of combretastatin A-4 and its apoptosis-inducing effects on lymphoma, leukemia and other tumor cells in vitro. RSC Med. Chem., 13 (9). S. 1044 - 1052. CAMBRIDGE: ROYAL SOC CHEMISTRY. ISSN 2632-8682

Full text not available from this repository.

Abstract

Hexacarbonyl[1,3-dimethoxy-5-((4 '-methoxyphenyl)ethynyl)benzene]dicobalt (NAHO27), an organometallic analogue of combretastatin A-4, has been synthesized and its activity against lymphoma, leukemia, breast cancer and melanoma cells has been investigated. It was shown that NAHO27 specifically induces apoptosis in BJAB lymphoma and Nalm-6 leukemia cells at low micromolar concentration and does not affect normal leukocytes in vitro. It also proved to be active against vincristine and daunorubicin resistant leukemia cell lines with p-glycoprotein-caused multidrug resistance and showed a pronounced (550%) synergistic effect when co-applied with vincristine at very low concentrations. Mechanistic investigations revealed NAHO27 to induce apoptosis via the mitochondrial (intrinsic) pathway as reflected by the processing of caspases 3 and 9, the involvement of Bcl-2 and smac/DIABLO, and the reduction of mitochondrial membrane potential. Gene expression analysis and protein expression analysis via western blot showed an upregulation of the proapoptotic protein harakiri by 9%.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Abodo Onambele, Liliane UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoffmann, Natalie UNSPECIFIED UNSPECIFIED UNSPECIFIED Kater, Lisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Hemmersbach, Lars UNSPECIFIED UNSPECIFIED UNSPECIFIED Neudorfl, Jorg-Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Sitnikov, Nikolay UNSPECIFIED UNSPECIFIED UNSPECIFIED Kater, Benjamin UNSPECIFIED UNSPECIFIED UNSPECIFIED Frias, Corazon UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmalz, Hans-Gunther UNSPECIFIED UNSPECIFIED UNSPECIFIED Prokop, Aram UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-681474
DOI:	10.1039/d2md00144f
Journal or Publication Title:	RSC Med. Chem.
Volume:	13
Number:	9
Page Range:	S. 1044 - 1052
Date:	2022
Publisher:	ROYAL SOC CHEMISTRY
Place of Publication:	CAMBRIDGE
ISSN:	2632-8682
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language COBALT-ALKYNE COMPLEXES; PROTEIN-SYNTHESIS; DEATH; INHIBITION; CHEMISTRY; AGENTS; MODE; ACID; A4 Multiple languages Biochemistry & Molecular Biology; Chemistry, Medicinal Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68147