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Theranostic Lysosomal Targeting Anticancer and Antimetastatic Agents: Half-Sandwich Iridium(III) Rhodamine Complexes

Identifieur interne : 000330 ( Main/Exploration ); précédent : 000329; suivant : 000331

Theranostic Lysosomal Targeting Anticancer and Antimetastatic Agents: Half-Sandwich Iridium(III) Rhodamine Complexes

Auteurs : Wenli Ma [République populaire de Chine] ; Xingxing Ge [République populaire de Chine] ; Zhishan Xu [République populaire de Chine] ; Shumiao Zhang [République populaire de Chine] ; Xiangdong He [République populaire de Chine] ; Juanjuan Li [République populaire de Chine] ; Xiaorong Xia [République populaire de Chine] ; Xiaobing Chen [République populaire de Chine] ; Zhe Liu [République populaire de Chine]

Source :

RBID : PMC:6751730

Abstract

Two rhodamine-modified half-sandwich Ir(III) complexes with the general formula [(Cpx)Ir(ĈN) Cl] were synthesized and characterized, where Cpx is 1-biphenyl-2,3,4,5-tetramethylcyclopentadienyl (Cpxbiph). Both complexes showed potent anticancer activity against A549, HeLa, and HepG2 cancer cells and normal cells, and altered ligands had an effect on proliferation resistance. The complex enters cells through energy dependence, and because of the different ligands, not only could it affect the anticancer ability of the complex but also could affect the degree of complex lysosome targeting, lysosomal damage, and further prove the antiproliferative mechanism of the complex. Excitingly, antimetastatic experiments demonstrated that complex 1 has the ability to block the migration of cancer cells. Furthermore, although the complex did not show a stronger ability to interfere with the coenzyme NAD+/NADH pair by transfer hydrogenation, the intracellular reactive oxygen species (ROS) content has shown a marked increase. NF-κB activity is increased by ROS regulation, and the role of ROS-NF-κB signaling pathway further induces apoptosis. Moreover, cell flow experiments also demonstrated that complex 1 blocked the cell cycle in S phase, but the complex did not cause significant changes in the mitochondrial membrane potential.


Url:
DOI: 10.1021/acsomega.9b01863
PubMed: 31552370
PubMed Central: 6751730


Affiliations:


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Le document en format XML

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, Qufu 273165,
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<p>Two rhodamine-modified half-sandwich Ir(III) complexes with the general formula [(Cp
<sup>x</sup>
)Ir(ĈN) Cl] were synthesized and characterized, where Cp
<sup>x</sup>
is 1-biphenyl-2,3,4,5-tetramethylcyclopentadienyl (Cp
<sup>xbiph</sup>
). Both complexes showed potent anticancer activity against A549, HeLa, and HepG2 cancer cells and normal cells, and altered ligands had an effect on proliferation resistance. The complex enters cells through energy dependence, and because of the different ligands, not only could it affect the anticancer ability of the complex but also could affect the degree of complex lysosome targeting, lysosomal damage, and further prove the antiproliferative mechanism of the complex. Excitingly, antimetastatic experiments demonstrated that complex
<bold>1</bold>
has the ability to block the migration of cancer cells. Furthermore, although the complex did not show a stronger ability to interfere with the coenzyme NAD
<sup>+</sup>
/NADH pair by transfer hydrogenation, the intracellular reactive oxygen species (ROS) content has shown a marked increase. NF-κB activity is increased by ROS regulation, and the role of ROS-NF-κB signaling pathway further induces apoptosis. Moreover, cell flow experiments also demonstrated that complex
<bold>1</bold>
blocked the cell cycle in S phase, but the complex did not cause significant changes in the mitochondrial membrane potential.</p>
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</record>

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