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Issue 13, 2019
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Impairment of the autophagy-related lysosomal degradation pathway by an anticancer rhenium(i) complex

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Abstract

Lysosomes play a critical role in the autophagy process. The impairment of lysosomes can affect the degradation of autophagic cargo, leading to the blockage of autophagy at the lysosomal stage and subsequent cell death. Herein, two phosphorescent Re(I) tricarbonyl complexes (Re1 and Re2) bearing β-carboline derivatives have been synthesized and characterized. Both complexes show pH-dependent phosphorescence, which can be used to specifically image the lysosomes. Cytotoxicity assay shows that they exhibit high anticancer activity and are able to overcome cross-resistance to cisplatin. Re2 can induce autophagy, which is blocked at the lysosomal stage due to lysosomal dysfunction, such as the decrease of cathepsin B activity, subsequently leading to both autophagy and apoptosis dependent cell death. In vivo studies revealed that it could significantly inhibit tumor growth.

Graphical abstract: Impairment of the autophagy-related lysosomal degradation pathway by an anticancer rhenium(i) complex

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Article information


Submitted
23 Jan 2019
Accepted
25 Feb 2019
First published
27 Feb 2019

Dalton Trans., 2019,48, 4398-4404
Article type
Paper

Impairment of the autophagy-related lysosomal degradation pathway by an anticancer rhenium(I) complex

L. He, Z. Pan, W. Qin, Y. Li, C. Tan and Z. Mao, Dalton Trans., 2019, 48, 4398
DOI: 10.1039/C9DT00322C

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