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

He Liang; Pan Zheng-Yin; Qin Wei-Wei; Li Yi; Tan Cai-Ping; Mao Zong-Wan

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

机译：抗癌铼（i）复合物的自噬相关溶酶体降解途径的损害

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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 -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.

机译：溶酶体在自噬过程中发挥着关键作用。溶酶体的损害可能影响自噬型货物的降解，导致溶酶体阶段和随后的细胞死亡堵塞自噬。这里，已经合成和表征了两种磷光Re（I）三羰基络合物（RE1和RE2）轴承 - 碳碱衍生物。两种复合物都显示pH依赖性磷光，其可用于特异性图像溶酶体。细胞毒性测定表明它们表明它们具有高抗癌活性，并且能够克服对顺铂的交叉抗性。 Re2可以诱导自噬，由于溶酶体功能障碍，例如组织蛋白酶B活性的减少，随后导致自噬和凋亡依赖性细胞死亡，抑制溶酶体阶段。体内研究表明，它可以显着抑制肿瘤生长。

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《Dalton transactions: An international journal of inorganic chemistry》 |2019年第13期|共7页
作者
He Liang; Pan Zheng-Yin; Qin Wei-Wei; Li Yi; Tan Cai-Ping; Mao Zong-Wan;
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作者单位

South China Agr Univ Coll Mat &

Energy Guangzhou 510642 Guangdong Peoples R China;

Sun Yat Sen Univ MOE Key Lab Bioinorgan &

Synthet Chem Sch Chem Guangzhou 510275 Guangdong Peoples R China;

South China Agr Univ Coll Mat &

Energy Guangzhou 510642 Guangdong Peoples R China;

Hunan Univ Sci &

Technol Key Lab Theoret Organ Chem &

Funct Mol Minist Educ Sch Chem &

Chem Engn Xiangtan 411201 Peoples R China;

Sun Yat Sen Univ MOE Key Lab Bioinorgan &

Synthet Chem Sch Chem Guangzhou 510275 Guangdong Peoples R China;

South China Agr Univ Coll Mat &

Energy Guangzhou 510642 Guangdong Peoples R China;

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正文语种 eng
中图分类化学;无机化学;
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1. Impairment of the autophagy-related lysosomal degradation pathway by an anticancer rhenium(i) complex [J] . He Liang, Pan Zheng-Yin, Qin Wei-Wei, Dalton transactions: An international journal of inorganic chemistry . 2019,第13期

机译：抗癌铼（i）复合物的自噬相关溶酶体降解途径的损害
2. Ubiquitination is associated with lysosomal degradation of cell surface-resident ATP-binding cassette transporter A1 (ABCA1) through the endosomal sorting complex required for transport (ESCRT) pathway. [J] . Mizuno T, Hayashi H, Naoi S, Hepatology: Official Journal of the American Association for the Study of Liver Diseases . 2011,第2期

机译：泛素化与通过运输（ESCRT）途径所需的内体分选复合体的细胞表面驻留ATP结合盒转运蛋白A1（ABCA1）的溶酶体降解有关。
3. SEC hyphenated to a multielement-specific detector unravels the degradation pathway of a bimetallic anticancer complex in human plasma [J] . Sarpong-Kumankomah Sophia, Contel Maria, Gailer Juergen Journal of chromatography, B. Analytical technologies in the biomedical and life sciences . 2020,第期

机译：秒将以多元素特异性探测器连字符无助地在人血浆中的双金属抗癌复合物的降解途径
4. Lysosomal Photodamage Induces Cell Death via Mitochondrial Apoptotic Pathway [C] . Lei Liu, Xian-wang Wang, Hui Li Optical trapping and microscopic imaging . 2009

机译：溶酶体光损伤通过线粒体凋亡途径诱导细胞死亡。
5. I. Symmetrical ligand bridged bimetallic complexes of rhenium(I): Implications for electrocatalytic reduction of carbon dioxide. II. Unimolecular excited state relaxation pathways in polypyridyl complexes of rhenium(I). [D] . Baiano, John Augustus. 1992

机译：I. ligand的对称配体桥联双金属络合物（I）：对电催化还原二氧化碳的影响。二。 poly（I）聚吡啶配合物中的单分子激发态弛豫途径。
6. The Endosomal Sorting Complex Required for Transport Pathway Mediates Chemokine Receptor CXCR4-promoted Lysosomal Degradation of the Mammalian Target of Rapamycin Antagonist DEPTOR [O] . Rita Verma, Adriano Marchese 2015

机译：运输途径所需的内体分选复合体介导雷帕霉素拮抗剂DEPTOR的趋化因子受体CXCR4促进溶酶体降解的哺乳动物目标。
7. Ubiquitination is associated with lysosomal degradation of cell surface-resident ATP-binding cassette transporter A1 (ABCA1) through the endosomal sorting complex required for transport (ESCRT) pathway [O] . Tadahaya Mizuno, Hisamitsu Hayashi, Sotaro Naoi, 2011

机译：泛素化与细胞表面驻留ATP结合盒转运蛋白A1（ABCA1）的溶酶体降解通过转运（ESCRT）途径所需的内体分选复合物相关

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

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