PMID- 35155187 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220216 IS - 2234-943X (Print) IS - 2234-943X (Electronic) IS - 2234-943X (Linking) VI - 11 DP - 2021 TI - Ethyl Ferulate Suppresses Esophageal Squamous Cell Carcinoma Tumor Growth Through Inhibiting the mTOR Signaling Pathway. PG - 780011 LID - 10.3389/fonc.2021.780011 [doi] LID - 780011 AB - Ethyl ferulate is a phenylpropanoid compound isolated from the medicinal herb Ferula. Although ethyl ferulate has anti-inflammatory, antioxidant, and neuroprotective activities with potential use in the nutraceutical and pharmaceutical industry, its anticancer effects and underlying molecular mechanisms against esophageal squamous cell carcinoma (ESCC) have not been investigated. This study investigates the anticancer activity and molecular mechanism of ethyl ferulate in ESCC. MTT, focus formation, soft agar, and cell cycle analysis were used to determine the effect of ethyl ferulate on cell proliferation and cell cycle. Potential candidate proteins were screened and verified via Western blotting, in vitro kinase assay, and in vitro pull-down assay. Mammalian target of rapamycin (mTOR) knockdown cell lines were established by lentiviral infection with shmTOR. The effect of ethyl ferulate on tumor growth was assessed using ESCC patient-derived xenograft models. Ethyl ferulate significantly inhibited cell growth and induced G1 phase cell cycle arrest in ESCC cells. Ethyl ferulate reduced the activity of mTOR in vitro. The inhibition of ESCC cell growth by ethyl ferulate is dependent on mTOR expression. In addition, ethyl ferulate strongly reduced ESCC patient-derived xenograft tumor growth in an in vivo mouse model. Ethyl ferulate is an mTOR inhibitor that can suppress ESCC progression and may be a novel candidate compound for esophageal cancer chemoprevention. CI - Copyright (c) 2022 Pang, Xie, Zhang, Laster, Liu and Kim. FAU - Pang, Mengjun AU - Pang M AD - The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China. AD - China-US (Henan) Hormel Cancer Institute, Zhengzhou, China. FAU - Xie, Xiaomeng AU - Xie X AD - The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China. AD - China-US (Henan) Hormel Cancer Institute, Zhengzhou, China. FAU - Zhang, Yuanyuan AU - Zhang Y AD - China-US (Henan) Hormel Cancer Institute, Zhengzhou, China. AD - Translational Research Institute, Henan Provincial People's Hospital, Academy of Medical Science, Zhengzhou University, Zhengzhou, China. FAU - Laster, Kyle Vaughn AU - Laster KV AD - China-US (Henan) Hormel Cancer Institute, Zhengzhou, China. FAU - Liu, Kangdong AU - Liu K AD - The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China. AD - China-US (Henan) Hormel Cancer Institute, Zhengzhou, China. AD - Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, China. AD - The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, China. AD - International Joint Research Center of Cancer Chemoprevention, Zhengzhou, China. FAU - Kim, Dong Joon AU - Kim DJ AD - The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China. AD - China-US (Henan) Hormel Cancer Institute, Zhengzhou, China. AD - The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, China. LA - eng PT - Journal Article DEP - 20220128 PL - Switzerland TA - Front Oncol JT - Frontiers in oncology JID - 101568867 PMC - PMC8833257 OTO - NOTNLM OT - cancer growth OT - esophageal squamous cell carcinoma OT - ethyl ferulate OT - mTOR OT - patient-derived xenograft COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/02/15 06:00 MHDA- 2022/02/15 06:01 PMCR- 2021/01/01 CRDT- 2022/02/14 05:34 PHST- 2021/09/20 00:00 [received] PHST- 2021/12/27 00:00 [accepted] PHST- 2022/02/14 05:34 [entrez] PHST- 2022/02/15 06:00 [pubmed] PHST- 2022/02/15 06:01 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fonc.2021.780011 [doi] PST - epublish SO - Front Oncol. 2022 Jan 28;11:780011. doi: 10.3389/fonc.2021.780011. eCollection 2021.