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Mono- and Dinuclear Phosphorescent Rhenium(I) Complexes: Impact of Subcellular Localization on Anticancer Mechanisms.
Chemistry. 2016 06 01; 22(23):7800-9.C

Abstract

Elucidation of relationship among chemical structure, cellular uptake, localization, and biological activity of anticancer metal complexes is important for the understanding of their mechanisms of action. Organometallic rhenium(I) tricarbonyl compounds have emerged as potential multifunctional anticancer drug candidates that can integrate therapeutic and imaging capabilities in a single molecule. Herein, two mononuclear phosphorescent rhenium(I) complexes (Re1 and Re2), along with their corresponding dinuclear complexes (Re3 and Re4), were designed and synthesized as potent anticancer agents. The subcellular accumulation of Re1-Re4 was conveniently analyzed by confocal microscopy in situ in live cells by utilizing their intrinsic phosphorescence. We found that increased lipophilicity of the bidentate ligands could enhance their cellular uptake, leading to improved anticancer efficacy. The dinuclear complexes were more potent than the mononuclear counterparts. The molecular anticancer mechanisms of action evoked by Re3 and Re4 were explored in detail. Re3 with a lower lipophilicity localizes to lysosomes and induces caspase-independent apoptosis, whereas Re4 with higher lipophilicity specially accumulates in mitochondria and induces caspase-independent paraptosis in cancer cells. Our study demonstrates that subcellular localization is crucial for the anticancer mechanisms of these phosphorescent rhenium(I) complexes.

Authors+Show Affiliations

MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, 510275, P.R. China.MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, 510275, P.R. China. cesmzw@mail.sysu.edu.cn.MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, 510275, P.R. China.MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, 510275, P.R. China.MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, 510275, P.R. China.MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, 510275, P.R. China. tancaip@mail.sysu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27106876

Citation

Ye, Rui-Rong, et al. "Mono- and Dinuclear Phosphorescent Rhenium(I) Complexes: Impact of Subcellular Localization On Anticancer Mechanisms." Chemistry (Weinheim an Der Bergstrasse, Germany), vol. 22, no. 23, 2016, pp. 7800-9.
Ye RR, Tan CP, Chen MH, et al. Mono- and Dinuclear Phosphorescent Rhenium(I) Complexes: Impact of Subcellular Localization on Anticancer Mechanisms. Chemistry. 2016;22(23):7800-9.
Ye, R. R., Tan, C. P., Chen, M. H., Hao, L., Ji, L. N., & Mao, Z. W. (2016). Mono- and Dinuclear Phosphorescent Rhenium(I) Complexes: Impact of Subcellular Localization on Anticancer Mechanisms. Chemistry (Weinheim an Der Bergstrasse, Germany), 22(23), 7800-9. https://doi.org/10.1002/chem.201505160
Ye RR, et al. Mono- and Dinuclear Phosphorescent Rhenium(I) Complexes: Impact of Subcellular Localization On Anticancer Mechanisms. Chemistry. 2016 06 1;22(23):7800-9. PubMed PMID: 27106876.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mono- and Dinuclear Phosphorescent Rhenium(I) Complexes: Impact of Subcellular Localization on Anticancer Mechanisms. AU - Ye,Rui-Rong, AU - Tan,Cai-Ping, AU - Chen,Mu-He, AU - Hao,Liang, AU - Ji,Liang-Nian, AU - Mao,Zong-Wan, Y1 - 2016/04/23/ PY - 2015/12/25/received PY - 2016/4/24/entrez PY - 2016/4/24/pubmed PY - 2017/12/13/medline KW - antitumor agents KW - ligands KW - lipophilicity KW - phosphorescence KW - rhenium SP - 7800 EP - 9 JF - Chemistry (Weinheim an der Bergstrasse, Germany) JO - Chemistry VL - 22 IS - 23 N2 - Elucidation of relationship among chemical structure, cellular uptake, localization, and biological activity of anticancer metal complexes is important for the understanding of their mechanisms of action. Organometallic rhenium(I) tricarbonyl compounds have emerged as potential multifunctional anticancer drug candidates that can integrate therapeutic and imaging capabilities in a single molecule. Herein, two mononuclear phosphorescent rhenium(I) complexes (Re1 and Re2), along with their corresponding dinuclear complexes (Re3 and Re4), were designed and synthesized as potent anticancer agents. The subcellular accumulation of Re1-Re4 was conveniently analyzed by confocal microscopy in situ in live cells by utilizing their intrinsic phosphorescence. We found that increased lipophilicity of the bidentate ligands could enhance their cellular uptake, leading to improved anticancer efficacy. The dinuclear complexes were more potent than the mononuclear counterparts. The molecular anticancer mechanisms of action evoked by Re3 and Re4 were explored in detail. Re3 with a lower lipophilicity localizes to lysosomes and induces caspase-independent apoptosis, whereas Re4 with higher lipophilicity specially accumulates in mitochondria and induces caspase-independent paraptosis in cancer cells. Our study demonstrates that subcellular localization is crucial for the anticancer mechanisms of these phosphorescent rhenium(I) complexes. SN - 1521-3765 UR - https://www.unboundmedicine.com/medline/citation/27106876/Mono__and_Dinuclear_Phosphorescent_Rhenium_I__Complexes:_Impact_of_Subcellular_Localization_on_Anticancer_Mechanisms_ L2 - https://doi.org/10.1002/chem.201505160 DB - PRIME DP - Unbound Medicine ER -