Proteomics

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Proteomics reveals the inhibitory mechanism of Levodopa against esophageal squamous cell carcinoma


ABSTRACT: The high recurrence rate and poor survival prospects of esophageal squamous cell carcinoma (ESCC) patients after treatment make the ongoing research on chemoprevention drugs for ESCC particularly important. In helping to solve this problem, we screened a large number of FDA-approved drugs and found that levodopa, a drug used to treat Parkinson’s disease, has an inhibitory effect on the growth of ESCC cells. To elucidate the molecular mechanisms, we applied mass spectrometry to investigate the anti-tumor activity of levodopa on ESCC. The results suggest that levodopa can down-regulate oxidative phosphorylation, non-alcoholic fatty liver disease (NAFLD) and parkinson disease pathways. SDHD, NDUFS4 and MT-CO3, major respiratory compounds in the mitochondria, were involved in these pathways. Down-regulation of these proteins is associated with mitochondrial dysfunction. Western blotting and immunofluorescence results confirmed the authenticity of proteomics data. Cell viability assay revealed that mitochondrial activity had been suppressed after levodopa treatment. Mitochondrial membrane potential reduction was detected by JC-1 and TMRE assays. And transmission electron microscope (TEM) analysis indicated that mitochondrial morphology changed. Taken together, levodopa inhibits the growth of ESCC through restraining the mitochondria.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: xiaomei li  

LAB HEAD: Kangdong Liu

PROVIDER: PXD013824 | Pride | 2021-09-08

REPOSITORIES: Pride

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Publications

Proteomics Reveal the Inhibitory Mechanism of Levodopa Against Esophageal Squamous Cell Carcinoma.

Li Zhenzhen Z   Li Xin X   He Xinyu X   Jia Xuechao X   Zhang Xiaofan X   Lu Bingbing B   Zhao Jimin J   Lu Jing J   Chen Lexia L   Dong Ziming Z   Liu Kangdong K   Dong Zigang Z  

Frontiers in pharmacology 20200925


High recurrence rates and poor survival of patients with esophageal squamous cell carcinoma (ESCC) after treatment make ongoing research on chemoprevention drugs for ESCC particularly important. In this study, we screened a large number of FDA-approved drugs and found levodopa, a drug used to treat Parkinson's disease, had an inhibitory effect on the growth of ESCC cells. To elucidate the molecular mechanisms involved, we applied quantitative proteomics to investigate the anti-tumor activity of  ...[more]

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