High-Dose NMN Shows Promise in Inhibiting Lung Adenocarcinoma Growth
Introduction: Aging is associated with functional decline and an increased risk of age-related diseases, prompting the search for anti-aging interventions. Nicotinamide mononucleotide (NMN), a biologically active nucleotide, is currently being investigated as a potential anti-aging drug. NMN is a precursor to nicotinamide adenine dinucleotide (NAD) and plays a role in cellular metabolism. While the use of NMN in age-related diseases has been explored, few studies have investigated its effects on tumors. Nevertheless, this article sheds light on the potential of NMN, particularly at high doses, in manipulating cancer cell metabolism and its therapeutic implications for lung adenocarcinoma.
Understanding NMN and its Effects on Lung Adenocarcinoma:
NMN is believed to increase cellular levels of NAD, which is involved in cellular metabolism. High-dose NMN leads to the production of excess nicotinamide (NAM) through metabolism. Overexpression of nicotinamide phosphoribosyltransferase (NAMPT) decreases intracellular NAM levels and promotes cell proliferation. High-dose NMN promotes ferroptosis, an iron-dependent form of cell death, through NAM-mediated SIRT1-AMPK-ACC signaling.
- In vitro and in vivo experiments demonstrated that high-dose NMN inhibits lung adenocarcinoma growth.
- This tumor suppressive ability is attributed to NMN's promotion of ferroptosis through NAM-mediated SIRT1-AMPK-ACC signaling.
- NMN treatment at high doses resulted in the overload of NAM, suppressing lung adenocarcinoma growth.
- The study also investigated the combinatory effects of NMN with other inhibitors, showing increased efficacy in tumor suppression.
Various assays were conducted, including cell culture, lentivirus construction and infection, Western blot assays, cell proliferation assays, apoptosis assays, xenograft assays in mice, and analyses of cellular structure, reactive oxygen species (ROS) levels, lipid peroxidation, and glutathione levels. Statistical analyses were performed to validate the findings.
The study highlights the potential of high-dose NMN in inhibiting lung adenocarcinoma growth through the induction of ferroptosis. This research underscores the importance of considering the dose and compatibility with other drugs in using NMN for lung adenocarcinoma patients. Further optimization of NMN responses in lung adenocarcinoma patients warrants exploration.
Supplementary Materials and Funding:
Supplementary materials containing additional data are available for download through a provided link. The study received partial support from the National Natural Science Foundation of China.
Author Contributions, Animal Experiments, and Data Availability:
The work was designed by J.W, M.Z., and S.W. Data analysis and interpretation were performed by M.Z., J.C., H.C., Y.W., and S.S. The manuscript was drafted by M.Z. and J.C. with critical revisions from F.Z., Q.C., S.W., and J.W. Animal experiments were conducted with approval from the Institutional Animal Care and Use Committee of Nanjing Medical University. The raw data is available with the consent of the corresponding author, who is responsible for granting access.
Conflicts of Interest:
The authors declare no conflicts of interest, ensuring the transparency and credibility of their work. MDPI and/or the editor(s) also do not take responsibility for any injury to people or property resulting from the ideas, methods, instructions, or products mentioned in the content.
In summary, high-dose NMN treatment shows promise in inhibiting lung adenocarcinoma growth through the promotion of ferroptosis. This study opens new perspectives on clinical therapy for lung adenocarcinoma and warrants further investigation into the optimal use of NMN in cancer treatment.
Title of paper: High-Dosage NMN Promotes Ferroptosis to Suppress Lung Adenocarcinoma Growth through the NAM-Mediated SIRT1-AMPK-ACC Pathway
Author(s): Zhang M, Cui J, Chen H, Wang Y, Kuai X, Sun S, Tang Q, Zong F, Chen Q, Wu J, Wu S.
Year published: 2023
Published in: Cancers (Basel)
Original article can be found here.