1. Curcumin Reverses NNMT-Induced 5-Fluorouracil Resistance via Increasing ROS and Cell Cycle Arrest in Colorectal Cancer Cells.
- Author
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Li G, Fang S, Shao X, Li Y, Tong Q, Kong B, Chen L, Wang Y, Yang J, Yu H, Xie X, and Zhang J
- Subjects
- Animals, Apoptosis drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Down-Regulation drug effects, Drug Synergism, Humans, Inhibitory Concentration 50, Male, Mice, Inbred BALB C, Mice, Nude, Phosphorylation drug effects, STAT3 Transcription Factor metabolism, Xenograft Model Antitumor Assays, Mice, Cell Cycle Checkpoints drug effects, Colorectal Neoplasms enzymology, Colorectal Neoplasms pathology, Curcumin pharmacology, Fluorouracil pharmacology, Nicotinamide N-Methyltransferase metabolism, Reactive Oxygen Species metabolism
- Abstract
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.
- Published
- 2021
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