ReferenceID 5386

Harmaline isolated from Peganum harmala suppresses growth of esophageal squamous cell carcinoma through targeting mTOR

Phytother Res

Harmaline is a naturally occurring beta-carboline alkaloid that is isolated from Peganum harmala. It has shown efficacy in treating Parkinson's disease and has been reported to exhibit antimicrobial and anticancer proper

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Reference Id
5386
Evidence Id
21976
Core Evidence Id
21976
Source Reference Id
4030
Herb2 Reference Id
HBREF004827
Subject Paper Key
HBIN028799_34545650
Pubmed Id
34545650
Doi
10.1002/ptr.7289
Paper Title
Harmaline isolated from Peganum harmala suppresses growth of esophageal squamous cell carcinoma through targeting mTOR
Paper Abstract
Harmaline is a naturally occurring beta-carboline alkaloid that is isolated from Peganum harmala. It has shown efficacy in treating Parkinson's disease and has been reported to exhibit antimicrobial and anticancer properties. However, the molecular mechanism of harmaline in the context of esophageal squamous cell carcinoma (ESCC) has not been characterized. Here, we report that harmaline attenuates ESCC growth by directly targeting the mammalian target of rapamycin (mTOR). Harmaline strongly reduced cell proliferation and anchorage-independent cell growth. Additionally, harmaline treatment induced G2/M phase cell-cycle arrest through upregulation of p27. The results of in vitro and cell-based assays showed that harmaline directly inhibited the activity of mTOR kinase and the phosphorylation of its downstream pathway components. Depletion of mTOR using an shRNA-mediated strategy in ESCC cell lines indicated that reduced mTOR protein expression levels are correlated with decreased cell proliferation. Additionally, we observed that the inhibitory effect of harmaline was dependent upon mTOR expression. Notably, oral administration of harmaline suppressed ESCC patient-derived tumor growth in vivo. Taken together, harmaline is a potential mTOR inhibitor that might be used for therapeutically treating ESCC.
Journal
Phytother Res
Publish Year
2021
Experiment Subject
patient; escc cell lines
Experiment Type
Cell Experiment
Phenotype Related
Parkinson's Disease; Tumor; Esophageal Squamous Cell Carcinoma
Paper Title Cn
Paper Title En
Harmaline isolated from Peganum harmala suppresses growth of esophageal squamous cell carcinoma through targeting mTOR
Bilingual Status
semi_complete