Cancer Reports (Mar 2023)

Anti‐cancer effect of entacaponeon esophageal cancer cells via apoptosis induction and cell cycle modulation

  • Fahimeh Ramedani,
  • Seyyed Mehdi Jafari,
  • Marie Saghaeian Jazi,
  • Zeinab Mohammadi,
  • Jahanbakhsh Asadi

DOI
https://doi.org/10.1002/cnr2.1759
Journal volume & issue
Vol. 6, no. 3
pp. n/a – n/a

Abstract

Read online

Abstract Background Esophageal cancer (EC) is the sixth leading cause of cancer‐related death, despite many advances in treatment, the survival of patients still remains poor. In recent years, the N6‐methyladenosine (m6A) has been introduced as one of the most important modifications at the epitranscriptome level, with an important role in the mRNA regulation in various diseases, such as cancers. The m6A is regulated by different factors, including FTO as a demethylase. The m6A modification, especially through FTO overexpression has an oncogenic role in different cancer types such as EC. Recent studies showed that entacapone, a catechol‐o‐methyl transferase (COMT) inhibitor currently applied for Parkinson's disease, can inhibit FTO enzyme. Aims In this study, we aimed to investigate the effect of entacapone as an FTO inhibitor on the m6A level and also apoptosis and cell cycle response in KYSE‐30 and YM‐1 of esophageal squamous cancer cell (ESCC) lines. Methods Cell toxicity and IC50 of entacapone were evaluated using The MTT assay in YM‐1 and KYSE‐30 cells. Cells were treated into two groups: DMSO (control) and entacapone (mean IC50). Total RNA was extracted, and m6A levels were measured via the ELISA method. Subsequently, the apoptosis and cell cycle dys‐regulation were detected by annexin‐V‐FITC/PI staining and PI staining via flow cytometry. Results Entacapone has the cytotoxicity effect on both esophageal cancer cell lines compared to normal PBMC cells. As well, entacapone treatment (140 μM) can induce apoptosis (KYSE‐30: 50%. YM‐1:22.6%) and has a modulatory effect on cell cycle progression in both YM‐1 and KYSE‐30 cells (p‐value<.05). However, no significant difference in the m6A concentration was observed. Conclusion Our findings suggested that entacapone has the inhibitory effect on ESCC cell lines through induction of the apoptosis and modulation of the cell cycle without toxicity on the normal PBMC.

Keywords