Curcumin Reverses NNMT-Induced 5-Fluorouracil Resistance via Increasing ROS and Cell Cycle Arrest in Colorectal Cancer Cells

被引：52

作者：

Li, Guoli ^{[1
,2
]}

Fang, Sining ^{[1
,2
]}

Shao, Xiao ^{[1
,2
]}

Li, Yejia ^{[1
,2
]}

Tong, Qingchao ^{[1
,2
]}

Kong, Beibei ^{[1
,2
]}

Chen, Lifen ^{[1
,2
]}

Wang, Yanzhong ^{[1
,2
]}

Yang, Jun ^{[1
,2
]}

Yu, Haitao ^{[1
,2
]}

Xie, Xinyou ^{[1
,2
]}

Zhang, Jun ^{[1
,2
]}

机构：

[1] Zhejiang Univ, Sir Run Run Shaw Hosp, Sch Med, Dept Clin Lab, Hangzhou 310016, Peoples R China

[2] Key Lab Precis Med Diag & Monitoring Res Zhejiang, Hangzhou 310016, Peoples R China

来源：

BIOMOLECULES | 2021年 / 11卷 / 09期

基金：

中国国家自然科学基金;

关键词：

nicotinamide N-methyltransferase; chemoresistance; curcumin; cell cycle arrest; colorectal cancer; NICOTINAMIDE N-METHYLTRANSFERASE; APOPTOSIS; CYTOTOXICITY; PROGRESSION; MECHANISMS; EXPRESSION; PATHWAY;

D O I：

10.3390/biom11091295

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Nicotinamide N-methyltransferase (NNMT) plays multiple roles in improving the aggressiveness of colorectal cancer (CRC) and enhancing resistance to 5-Fluorouracil (5-FU), making it an attractive therapeutic target. Curcumin (Cur) is a promising natural compound, exhibiting multiple antitumor effects and potentiating the effect of 5-FU. The aim of the present study is to explore the effect of Cur on attenuating NNMT-induced resistance to 5-FU in CRC. A panel of CRC cell lines with different NNMT expressions are used to characterize the effect of Cur. Herein, it is observed that Cur can depress the expression of NNMT and p-STAT3 in CRC cells. Furthermore, Cur can induce inhibition of cell proliferation, G2/M phase cell cycle arrest, and reactive oxygen species (ROS) generation, especially in high-NNMT-expression CRC cell lines. Cur can also re-sensitize high-NNMT-expression CRC cells to 5-FU both in vitro and in vivo. In summary, it is proposed that Cur can reverse NNMT-induced cell proliferation and 5-FU resistance through ROS generation and cell cycle arrest. Given that Cur has long been used, we suppose that Cur is a promising anticancer drug candidate with minimal side effects for human CRC therapy and can attenuate NNMT-induced resistance to 5-FU.

引用

页数：19

共 42 条

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