Curcumin Inhibits Viability of Clear Cell Renal Cell Carcinoma by Down-Regulating ADAMTS18 Gene Methylation though NF-κ B and AKT Signaling Pathway.
10.1007/s11655-021-3445-z
- Author:
Ben XU
1
;
Yi-Ji PENG
2
;
Wei-Jie ZHU
2
Author Information
1. Department of Urology, Peking University First Hospital and Institute of Urology, Peking University, National Urological Cancer Center, Beijing, 100034, China. xuben_pku@sina.com.
2. Department of Urology, Peking University First Hospital and Institute of Urology, Peking University, National Urological Cancer Center, Beijing, 100034, China.
- Publication Type:Journal Article
- Keywords:
ADAMTS18 gene;
clear cell renal cell carcinoma;
curcumin;
methylation;
signaling pathway
- MeSH:
ADAMTS Proteins/metabolism*;
Carcinoma, Renal Cell/pathology*;
Cell Line, Tumor;
Curcumin/pharmacology*;
DNA Methylation;
Female;
Humans;
Kidney Neoplasms/genetics*;
Male;
Matrix Metalloproteinase 2/metabolism*;
NF-kappa B/metabolism*;
Proto-Oncogene Proteins c-akt/metabolism*;
Signal Transduction
- From:
Chinese journal of integrative medicine
2022;28(5):419-424
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:To investigate the effect of curcumin on viability of clear cell renal cell carcinoma (ccRCC) and analyze its possible mechanism.
METHODS:In cell lines of A498 and 786-O, the effects of curcumin (1.25, 2.5, 5 and 10 μ mol/L) on the viability of ccRCC were analyzed at 24, 48 and 72 h by MTT assay. The protein expression levels of ADAMTS18 gene, p65, phosphorylation p65 (pp65), AKT, phosphorylation AKT (pAKT) and matrix metallopeptidase 2 (MMP-2) before and after curcumin (10 μ mol/L) treatment were examined by Western blotting. Real-time PCR and methylation specific PCR (MSP) were applied to analyze the expression and methylation level of ADAMTS18 gene before and after curcumin treatment (10 μ mol/L).
RESULTS:Curcumin significantly inhibited the viability of A498 and 786-O cell lines in a dose- and time-dependent manner (P<0.01). Up-regulation of ADAMTS18 gene expression with down-regulation of ADAMTS18 gene methylation was reflected after curcumin treatment, accompanied by down-regulation of nuclear factor κ B (NF-κ kB) related protein (p65 and pp65), AKT related protein (AKT and pAKT), and NF-κ B/AKT common related protein MMP-2. With ADAMTS18 gene overexpressed, the expression levels of p65, AKT and MMP2 were downregulated, of which were conversely up-regulated in silenced ADAMTS18 (sh-ADAMTS18). The expression of pp65, pAKT and MMP2 in sh-ADAMTS18 was down-regulated after being treated with PDTC (NF-κ B inhibitor) and LY294002 (AKT inhibitor).
CONCLUSIONS:Curcumin could inhibit the viability of ccRCC by down-regulating ADAMTS18 gene methylation though NF-κ B and AKT signaling pathway.
