High-Dosage NMN Promotes Ferroptosis to Suppress Lung Adenocarcinoma Growth through the NAM-Mediated SIRT1–AMPK–ACC Pathway
Background: Nicotinamide mononucleotide (NMN) is the physiological circulating NAD precursor thought to elevate the cellular level of NAD<sup>+</sup> and to ameliorate various age-related diseases. An inseparable link exists between aging and tumorigenesis, especially involving aberrant...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-04-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/15/9/2427 |
| _version_ | 1797602942418681856 |
|---|---|
| author | Mingjiong Zhang Jiahua Cui Haoyan Chen Yu Wang Xingwang Kuai Sibo Sun Qi Tang Feng Zong Qiaoyu Chen Jianqing Wu Shuangshuang Wu |
| author_facet | Mingjiong Zhang Jiahua Cui Haoyan Chen Yu Wang Xingwang Kuai Sibo Sun Qi Tang Feng Zong Qiaoyu Chen Jianqing Wu Shuangshuang Wu |
| author_sort | Mingjiong Zhang |
| collection | DOAJ |
| description | Background: Nicotinamide mononucleotide (NMN) is the physiological circulating NAD precursor thought to elevate the cellular level of NAD<sup>+</sup> and to ameliorate various age-related diseases. An inseparable link exists between aging and tumorigenesis, especially involving aberrant energetic metabolism and cell fate regulation in cancer cells. However, few studies have directly investigated the effects of NMN on another major ageing-related disease: tumors. Methods: We conducted a series of cell and mouse models to evaluate the anti-tumor effect of high-dose NMN. Transmission electron microscopy and a Mito-FerroGreen-labeled immunofluorescence assay (Fe<sup>2+</sup>) were utilized to demonstrate ferroptosis. The metabolites of NAM were detected via ELISA. The expression of the proteins involved in the SIRT1–AMPK–ACC signaling were detected using a Western blot assay. Results: The results showed that high-dose NMN inhibits lung adenocarcinoma growth in vitro and in vivo. Excess NAM is produced through the metabolism of high-dose NMN, whereas the overexpression of NAMPT significantly decreases intracellular NAM content, which, in turn, boosts cell proliferation. Mechanistically, high-dose NMN promotes ferroptosis through NAM-mediated SIRT1–AMPK–ACC signaling. Conclusions: This study highlights the tumor influence of NMN at high doses in the manipulation of cancer cell metabolism, providing a new perspective on clinical therapy in patients with lung adenocarcinoma. |
| first_indexed | 2024-03-11T04:23:40Z |
| format | Article |
| id | doaj.art-e0c8e72b46744ac29f567e0d386202e3 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T04:23:40Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-e0c8e72b46744ac29f567e0d386202e32023-11-17T22:39:35ZengMDPI AGCancers2072-66942023-04-01159242710.3390/cancers15092427High-Dosage NMN Promotes Ferroptosis to Suppress Lung Adenocarcinoma Growth through the NAM-Mediated SIRT1–AMPK–ACC PathwayMingjiong Zhang0Jiahua Cui1Haoyan Chen2Yu Wang3Xingwang Kuai4Sibo Sun5Qi Tang6Feng Zong7Qiaoyu Chen8Jianqing Wu9Shuangshuang Wu10Jiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, ChinaDepartment of Epidemiology, School of Public Health, Nantong University, Nantong 226019, ChinaJiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, ChinaJiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, ChinaDepartment of Pathology, Medical School, Nantong University, Nantong 226001, ChinaJiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, ChinaNHC Key Laboratory of Antibody Technique, Nanjing Medical University, Nanjing 210029, ChinaJiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, ChinaCentre for Assisted Reproduction, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200071, ChinaJiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, ChinaJiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, ChinaBackground: Nicotinamide mononucleotide (NMN) is the physiological circulating NAD precursor thought to elevate the cellular level of NAD<sup>+</sup> and to ameliorate various age-related diseases. An inseparable link exists between aging and tumorigenesis, especially involving aberrant energetic metabolism and cell fate regulation in cancer cells. However, few studies have directly investigated the effects of NMN on another major ageing-related disease: tumors. Methods: We conducted a series of cell and mouse models to evaluate the anti-tumor effect of high-dose NMN. Transmission electron microscopy and a Mito-FerroGreen-labeled immunofluorescence assay (Fe<sup>2+</sup>) were utilized to demonstrate ferroptosis. The metabolites of NAM were detected via ELISA. The expression of the proteins involved in the SIRT1–AMPK–ACC signaling were detected using a Western blot assay. Results: The results showed that high-dose NMN inhibits lung adenocarcinoma growth in vitro and in vivo. Excess NAM is produced through the metabolism of high-dose NMN, whereas the overexpression of NAMPT significantly decreases intracellular NAM content, which, in turn, boosts cell proliferation. Mechanistically, high-dose NMN promotes ferroptosis through NAM-mediated SIRT1–AMPK–ACC signaling. Conclusions: This study highlights the tumor influence of NMN at high doses in the manipulation of cancer cell metabolism, providing a new perspective on clinical therapy in patients with lung adenocarcinoma.https://www.mdpi.com/2072-6694/15/9/2427NMNNAMNAMPTferroptosislung adenocarcinoma |
| spellingShingle | Mingjiong Zhang Jiahua Cui Haoyan Chen Yu Wang Xingwang Kuai Sibo Sun Qi Tang Feng Zong Qiaoyu Chen Jianqing Wu Shuangshuang Wu High-Dosage NMN Promotes Ferroptosis to Suppress Lung Adenocarcinoma Growth through the NAM-Mediated SIRT1–AMPK–ACC Pathway Cancers NMN NAM NAMPT ferroptosis lung adenocarcinoma |
| title | High-Dosage NMN Promotes Ferroptosis to Suppress Lung Adenocarcinoma Growth through the NAM-Mediated SIRT1–AMPK–ACC Pathway |
| title_full | High-Dosage NMN Promotes Ferroptosis to Suppress Lung Adenocarcinoma Growth through the NAM-Mediated SIRT1–AMPK–ACC Pathway |
| title_fullStr | High-Dosage NMN Promotes Ferroptosis to Suppress Lung Adenocarcinoma Growth through the NAM-Mediated SIRT1–AMPK–ACC Pathway |
| title_full_unstemmed | High-Dosage NMN Promotes Ferroptosis to Suppress Lung Adenocarcinoma Growth through the NAM-Mediated SIRT1–AMPK–ACC Pathway |
| title_short | High-Dosage NMN Promotes Ferroptosis to Suppress Lung Adenocarcinoma Growth through the NAM-Mediated SIRT1–AMPK–ACC Pathway |
| title_sort | high dosage nmn promotes ferroptosis to suppress lung adenocarcinoma growth through the nam mediated sirt1 ampk acc pathway |
| topic | NMN NAM NAMPT ferroptosis lung adenocarcinoma |
| url | https://www.mdpi.com/2072-6694/15/9/2427 |
| work_keys_str_mv | AT mingjiongzhang highdosagenmnpromotesferroptosistosuppresslungadenocarcinomagrowththroughthenammediatedsirt1ampkaccpathway AT jiahuacui highdosagenmnpromotesferroptosistosuppresslungadenocarcinomagrowththroughthenammediatedsirt1ampkaccpathway AT haoyanchen highdosagenmnpromotesferroptosistosuppresslungadenocarcinomagrowththroughthenammediatedsirt1ampkaccpathway AT yuwang highdosagenmnpromotesferroptosistosuppresslungadenocarcinomagrowththroughthenammediatedsirt1ampkaccpathway AT xingwangkuai highdosagenmnpromotesferroptosistosuppresslungadenocarcinomagrowththroughthenammediatedsirt1ampkaccpathway AT sibosun highdosagenmnpromotesferroptosistosuppresslungadenocarcinomagrowththroughthenammediatedsirt1ampkaccpathway AT qitang highdosagenmnpromotesferroptosistosuppresslungadenocarcinomagrowththroughthenammediatedsirt1ampkaccpathway AT fengzong highdosagenmnpromotesferroptosistosuppresslungadenocarcinomagrowththroughthenammediatedsirt1ampkaccpathway AT qiaoyuchen highdosagenmnpromotesferroptosistosuppresslungadenocarcinomagrowththroughthenammediatedsirt1ampkaccpathway AT jianqingwu highdosagenmnpromotesferroptosistosuppresslungadenocarcinomagrowththroughthenammediatedsirt1ampkaccpathway AT shuangshuangwu highdosagenmnpromotesferroptosistosuppresslungadenocarcinomagrowththroughthenammediatedsirt1ampkaccpathway |