Parecoxib Enhances Resveratrol against Human Colorectal Cancer Cells through Akt and TXNDC5 Inhibition and MAPK Regulation
Journal
Nutrients
Journal Volume
16
Journal Issue
17
Start Page
3020
ISSN
2072-6643
Date Issued
2024-09
Author(s)
Chang, Wan-Ling
Peng, Jyun-Yu
Hong, Chain-Lang
Li, Pei-Ching
Chye, Soi Moi
Lu, Fung-Jou
Shih, Ching-Wei
Chen, Ching-Hsein
Abstract
In this study, we discovered the mechanisms underlying parecoxib and resveratrol combination's anti-cancer characteristics against human colorectal cancer DLD-1 cells. We studied its anti-proliferation and apoptosis-provoking effect by utilizing cell viability 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, fluorescence microscope, gene overexpression, Western blot, and flow cytometry analyses. Parecoxib enhanced the ability of resveratrol to inhibit cell viability and increase apoptosis. Parecoxib in combination with resveratrol strongly enhanced apoptosis by inhibiting the expression of thioredoxin domain containing 5 (TXNDC5) and Akt phosphorylation. Parecoxib enhanced resveratrol-provoked c-Jun -terminal kinase (JNK) and p38 phosphorylation. Overexpression of TXNDC5 and repression of JNK and p38 pathways significantly reversed the inhibition of cell viability and stimulation of apoptosis by the parecoxib/resveratrol combination. This study presents evidence that parecoxib enhances the anti-cancer power of resveratrol in DLD-1 colorectal cancer cells via the inhibition of TXNDC5 and Akt signaling and enhancement of JNK/p38 MAPK pathways. Parecoxib may be provided as an efficient drug to sensitize colorectal cancer by resveratrol.
Subjects
Akt
MAPK
TXNDC5
apoptosis
colorectal cancer
parecoxib
resveratrol
SDGs
Type
journal article