Impairment of the autophagy-related lysosomal degradation pathway by an anticancer rhenium(i) complex.
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ID: 42708
2019
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.
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he2019impairmentdalton
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| Authors | He, Liang;Pan, Zheng-Yin;Qin, Wei-Wei;Li, Yi;Tan, Cai-Ping;Mao, Zong-Wan; |
| Journal | Dalton transactions (Cambridge, England : 2003) |
| Year | 2019 |
| DOI | 10.1039/c9dt00322c |
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