scholarly journals A Novel Organometallic Rhenium Salt: DNA-Binding and Cytotoxicity Studies on Pancreatic, Breast and Lymphoma Cancers

Author(s):  
Christopher C. Krauss ◽  
Birsen Y. Varisli ◽  
Angela J. Winstead ◽  
Paul T. Wilder ◽  
David J. Weber ◽  
...  

Abstract DNA-binding studies of a variety of rhenium(I) tricarbonyl complexes are known. Primarily the rhenium complexes bind to DNA through intercalation or minor groove or both. We synthesized a novel organometallic salt of the type, [Re(µ-H)Re]+[Re(µ-OR)3Re]-. The UV-vis and emission spectroscopic titrations and viscosity studies indicate that the salt binds to DNA through partial intercalation. A variety of mono-, di-, and trinuclear rhenium(I) carbonyl complexes are known to exhibit cytotoxicity against numerous cancer cell lines. Examples of the cytotoxicity of tetranuclear rhenium (I) tricarbonyl complexes are rare. We have found that the tetranuclear, novel organometallic salt is highly potent on numerous cancer cells. The IC50 values (concentrations required to induce 50% cell deaths) are 0.220 µM on BxPC-3 pancreatic cancer cells, 0.298 µM on estrogen receptor positive MCF-7 breast cancer cells, 0.948 µM on triple negative MDA-MB-231 breast cancer cells, and 0.300 µM on U-937 lymphoma cells.

2018 ◽  
Author(s):  
Benedikt Warth ◽  
Amelia Palermo ◽  
Nicholas J.W. Rattray ◽  
Nathan V Lee ◽  
Zhou Zhu ◽  
...  

SummaryPalbociclib, is a selective inhibitor of cyclin-dependent kinases 4 and 6 and used as a first-line treatment for patients with estrogen receptor positive breast cancer. It has been shown that patients have improved progression-free survival when treated in combination with fulvestrant, an estrogen receptor antagonist. However, the mechanisms for this survival advantage are not known. We sought to analyze metabolic and transcriptomic changes in MCF-7 adenocarcinoma breast cancer cells following single and combined treatments to determine if selective metabolic pathways are targeted during combination therapy. Our results showed that individually, the drugs caused metabolic disruption to the same metabolic pathways, however fulvestrant additionally attenuated the pentose phosphate pathway and the production of important coenzymes. A comprehensive effect was observed when the drugs were applied together, confirming the combinatory therapy′s synergism in the cell model. This study highlights the power of merging high-dimensional datasets to unravel mechanisms involved in cancer metabolism and therapy.Highlights○First study employing multi-omics to investigate combined therapy on breast cancer cells○Fulvestrant attenuates the pentose phosphate pathway and coenzyme production○Synergism of palbociclib and fulvestrant was confirmed in vitro○Altered key pathways have been identifiedeTOC BlurbJohnson et al. applied an innovative multi-omics approach to decipher metabolic pathways affected by single versus combination dosing of palbociclib and fulvestrant in estrogen receptor positive breast cancer. Key metabolites and genes were correlated within metabolic pathways and shown to be involved in the drugs′ synergism.


PLoS ONE ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. e0153684 ◽  
Author(s):  
Zahra Rasoulzadeh ◽  
Roya Ghods ◽  
Tohid Kazemi ◽  
Ebrahim Mirzadegan ◽  
Nassim Ghaffari-Tabrizi-Wizsy ◽  
...  

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