Apoptosis-independent organoruthenium anticancer complexes that overcome multidrug resistance: self-assembly and phenotypic screening strategies - Archive ouverte HAL Access content directly
Journal Articles Chemical Science Year : 2017

Apoptosis-independent organoruthenium anticancer complexes that overcome multidrug resistance: self-assembly and phenotypic screening strategies

(1) , (2) , (3, 4) , (5) , (1, 4)
1
2
3
4
5

Abstract

Multidrug resistance is a major impediment to chemotherapy and limits the efficacies of conventional anticancer drugs. A strategy to bypass multidrug resistance is to develop new drug candidates capable of inducing apoptosis-independent programmed cell death. However, cellular pathways implicated in alternative programmed cell death are not well-elucidated and multifactorial, making a target-based discovery approach a challenge. Here, we show that a coordination-directed three-component assembly and phenotypic screening strategy could be employed as a viable alternative for the identification of apoptosis-independent organoruthenium anticancer agents. Through an on-plate synthesis and screening of 195 organoruthenium complexes against apoptosis-sensitive and -resistant cancers, we identified two apoptosis-independent hits. Subsequent validation of the two hits showed a lack of induction of apoptotic biomarkers, a caspase-independent activity and an equal efficacy in both apoptosis-sensitive and -resistant colorectal cancers. This validated their apoptosis-independent modes-of-action, paving the way as potential candidates for the treatment of highly-refractory cancer phenotypes.
Fichier principal
Vignette du fichier
ChemSci2017Chow_et_al.pdf (1.08 Mo) Télécharger le fichier
Origin : Publication funded by an institution
Loading...

Dates and versions

inserm-02365265 , version 1 (15-11-2019)

Identifiers

Cite

Mun Juinn Chow, Mohammad Alfiean, Giorgia Pastorin, Christian Gaiddon, Wee Han Ang. Apoptosis-independent organoruthenium anticancer complexes that overcome multidrug resistance: self-assembly and phenotypic screening strategies. Chemical Science, 2017, 8 (5), pp.3641-3649. ⟨10.1039/c7sc00497d⟩. ⟨inserm-02365265⟩
27 View
44 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More