4.7 Article

Dehydroevodiamine inhibits lung metastasis by suppressing survival and metastatic abilities of colorectal cancer cells

期刊

PHYTOMEDICINE
卷 96, 期 -, 页码 -

出版社

ELSEVIER GMBH
DOI: 10.1016/j.phymed.2021.153809

关键词

Dehydroevodiamine; Colorectal cancer; Metastasis; Apoptosis; Autophagy; Cell cycle arrest

资金

  1. National Research Foundation of Korea (NRF) - Korea government (MSIT) [2018R1C1B6002722, 2019R1I1A3A01060998, 2021R1A2C4 002170]
  2. National Research Foundation of Korea [2019R1I1A3A01060998, 2018R1C1B6002722] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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The study found that dehydroevodiamine (DHE) has potential therapeutic effects on lung metastasis of colorectal cancer (CRC) and proliferation of CRC cells. DHE suppresses cell viability, induces apoptosis and autophagy, and regulates cell migration and invasion.
Background: Despite the rising 5-year survival rate of colorectal cancer (CRC) patients, the survival rate decreases as the stage progress, and a low survival rate is highly associated with metastasis. Purpose: The purpose of our study is to investigate the effect of dehydroevodiamine (DHE) on the lung metastasis of CRC and the proliferation of CRC cells. Study design: Cell death was confirmed after DHE treatment on several CRC cell lines. The mechanism of cell cytotoxicity was found using flow cytometry. After that, the expression of the proteins or mRNAs related to the cell cytotoxicity was confirmed. Also, anti-metastatic ability of DHE in CRC cells was measured by checking the expression of Epithelial to Mesenchymal Transition (EMT) markers. Lung metastasis mouse model was established, and DHE was administered orally for 14 days. Results: DHE suppressed the viability of HCT116, CT26, SW480, and LoVo cells. DHE treatment led to G2/M arrest via a reduction of cyclin B1/CDK1 and caspase-dependent apoptosis. It also induced autophagy by regulating LC3-II and beclin-1 expression. Additionally, migration and invasion of CRC cells were decreased by DHE through regulation of the expression of EMT markers. Oral administration of DHE could inhibit the lung metastasis of CT26 cells in an in vivo model. Conclusion: Our study demonstrated that DHE has a potential therapeutic effect on colorectal cancer metastasis.

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