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Abstract Title:

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

Abstract Source:

Phytother Res. 2021 Sep 20. Epub 2021 Sep 20. PMID: 34545650

Abstract Author(s):

Yuanyuan Zhang, Xiaodan Shi, Xiaomeng Xie, Kyle Vaughn Laster, Mengjun Pang, Kangdong Liu, Joonsung Hwang, Dong Joon Kim

Article Affiliation:

Yuanyuan Zhang

Abstract:

Harmaline is a naturally occurringβ-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 mTORprotein 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, harmalineis a potential mTOR inhibitor that might be used for therapeutically treating ESCC.

Study Type : In Vitro Study

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Sayer Ji
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