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.
Highlights
We previously reported that Nicotinamide N-methyltransferase (NNMT) could promote cell proliferation, reduce reactive oxygen species (ROS), accelerate cell cycle, inhibit cell apoptosis, and enhance resistance to 5-FU in human colorectal cancer (CRC)
We demonstrated that NNMT could promote cell growth, inhibit apoptosis, inhibit autophagy, and enhance chemoresistance in breast cancer [8,9,10]
A Cell-Counting Kit-8 (CCK-8) assay showed that the viability of CRC cells was inhibited by Cur, especially in high-NNMT-expression cell lines
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Colorectal cancer (CRC) is the second most common cause of cancerrelated death worldwide [1]. Chemotherapy is still a mainstay of CRC treatment, and adjuvant chemotherapy based on 5-fluorouracil (5-FU) can significantly improve the prognosis of CRC [2]. 5-FU resistance occurs in certain areas of CRC patients, which leads to poor clinical prognosis [3]. The discovery of drugs in possession of a potential synergistic effect with 5-FU is urgently required
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