Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 28, 2021; 27(16): 1805-1815
Published online Apr 28, 2021. doi: 10.3748/wjg.v27.i16.1805
Mitochondrial pathway of the lysine demethylase 5C inhibitor CPI-455 in the Eca-109 esophageal squamous cell carcinoma cell line
Xiao-Jie Xue, Fei-Rong Li, Jing Yu
Xiao-Jie Xue, Fei-Rong Li, Department of Clinical Laboratory, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi 435000, Hubei Province, China
Xiao-Jie Xue, Hubei Key Laboratory of Kidney Disease Pathogenesis and Intervention, Huangshi 435000, Hubei Province, China
Xiao-Jie Xue, Medical College, Wuhan University of Science and Technology, Wuhan 430081, Hubei Province, China
Jing Yu, Department of Laboratory Medicine, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430079, Hubei Province, China
Author contributions: Xue XJ analyzed the data, drafted the article, and contributed to study design; Li FR contributed to data gathering; Yu J contributed to study design, editing, and revising the paper; all authors read and approved the final manuscript.
Supported by Young Talents Project of Hubei Provincial Health Commission, No. WJ2019H449.
Institutional review board statement: The study was reviewed and approved by Hubei cancer hospital, Tongji Medical College, Huazhong University of Science and Technology (approval No. LLHBCH2020LW-027).
Conflict-of-interest statement: The authors declare that they have no competing interests..
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jing Yu, PhD, Doctor, Department of Laboratory Medicine, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 116 Zhuodaoquan South Road, Wuhan 430079, Hubei Province, China. yujings9774@sina.com.cn
Received: January 8, 2021
Peer-review started: January 8, 2021
First decision: February 11, 2021
Revised: February 14, 2021
Accepted: March 24, 2021
Article in press: March 24, 2021
Published online: April 28, 2021
Abstract
BACKGROUND

Esophageal cancer is a malignant tumor of the digestive tract that is difficult to diagnose early. CPI-455 has been reported to inhibit various cancers, but its role in esophageal squamous cell carcinoma (ESCC) is unknown.

AIM

To investigate the effects and mechanism of the lysine demethylase 5C inhibitor, CPI-455, on ESCC cells.

METHODS

A methyl tetrazolium assay was used to detect the inhibitory effect of CPI-455 on the proliferation of Eca-109 cells. Apoptosis, reactive oxygen species (ROS), and mitochondrial membrane potential were assessed by flow cytometry. Laser confocal scanning and transmission electron microscopy were used to observe changes in Eca-109 cell morphology. The protein expression of P53, Bax, lysine-specific demethylase 5C (KDM5C), cleaved Caspase-9, and cleaved Caspase-3 were assayed by western blotting.

RESULTS

Compared with the control group, CPI-455 significantly inhibited Eca-109 cell proliferation. Gemcitabine inhibited Eca-109 cell proliferation in a concentration- and time-dependent manner. CPI-455 caused extensive alteration of the mitochondria, which appeared to have become atrophied. The cell membrane was weakly stained and the cytoplasmic structures were indistinct and disorganized, with serious cavitation when viewed by transmission electron microscopy. The flow cytometry and western blot results showed that, compared with the control group, the mitochondrial membrane potential was decreased and depolarized in Eca-109 cells treated with CPI-455. CPI-455 significantly upregulated the ROS content, P53, Bax, Caspase-9, and Caspase-3 protein expression in Eca-109 cells, whereas KDM5C expression was downregulated.

CONCLUSION

CPI-455 inhibited Eca-109 cell proliferation via mitochondrial apoptosis by regulating the expression of related genes.

Keywords: Lysine-specific demethylase 5C, CPI-455, Esophageal squamous cell carcinoma, Caspase, P53

Core Tip: This study confirmed that the lysine demethylase 5C inhibitor CPI-455 inhibited the proliferation of Eca-109 esophageal squamous cell carcinoma cells. CPI-455 played a role in esophageal squamous cell carcinoma cells proliferation and invasion that may have been associated in part with p53, Bax, Caspase-9, and Caspase-3 expression. CPI-455 induced Eca-109 cell apoptosis via a mitochondria-mediated intrinsic apoptotic signaling pathway by regulating the expression of related genes.