In 2020, the number of new cases of breast cancer in women reached 2.26 million worldwide, surpassing lung cancer as the most common cancer globally [1]. There are different types of breast cancer based on the presence of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2) [2]. Different types of breast cancer require different treatment methods; for example, ER-positive breast cancer is usually treated with endocrine therapy.

Among all breast cancers, triple-negative breast cancer (TNBC), which is negative for ER, PR, and HER2 receptors, is the most difficult to treat and accounts for 15% of breast cancer cases. Because it lacks treatment targets, the usual treatment methods are ineffective, and chemotherapy is one of the few options. TNBC is more likely to metastasize than other types of breast cancer, is prone to early relapse, and has a shorter overall survival time, so new treatment methods are needed.

Previous studies have shown that NAD+ metabolism is related to cancer and plays a critical role in tumor formation and metastasis [3]. In addition, NAD+ is a substrate for sirtuins and PARPs, which can have pro-cancer or anti-cancer effects in different cellular and tissue environments.

To understand the role of NAD+ metabolism in TNBC, Professor Yongzhang Luo's team at Tsinghua University conducted research and published their findings in the top journal "Oncogene." They found that NMN can inhibit the growth and metastasis of TNBC tumors in mice, significantly improving the survival of mice with cancer, and may be a potential treatment method for breast cancer.

• NMN can slow down the growth and spread of breast cancer and prolong the survival of mice.

To induce triple-negative breast cancer (TNBC), researchers injected HCC1937 cancer cells into the inguinal mammary fat pad of NCG mice. Subsequently, mice were injected with 500mg/kg of NMN daily. After 48 days, it was found that the tumor volume in the NMN group was 10% smaller than that in the control group.

In addition, H&E staining showed that the lung metastasis area in the NMN group was smaller, indicating that NMN can significantly inhibit the growth and metastasis of TNBC tumors. The researchers also found that the average lifespan of mice in the NMN group was extended by 15%, indicating that NMN can improve the survival of mice with TNBC after inhibiting the proliferation of cancer cells.

• NMN can activate SIRT1 to inhibit cancer cell metastasis.

NMN is a precursor of NAD+ and can significantly increase NAD+ levels, thereby activating the longevity protein SIRT1. SIRT1 is responsible for repairing DNA and eliminating reactive oxygen species (ROS) in cells. Therefore, the research team speculated that the anti-breast cancer benefits of NMN are due to the activation of SIRT1. By testing, it was found that the level of SIRT1 in TNBC tumors was lower than that in normal human breast epithelial cells, which further supported the researchers' speculation.

To verify this hypothesis, researchers knocked out SIRT1-related genes and found that without this protein, NMN cannot inhibit the metastasis and growth of TNBC. This indicates that NMN can indeed inhibit cancer metastasis by activating SIRT1. Researchers further studied the mechanism by which SIRT1 inhibits tumors and found that it is related to SIRT1 reducing the phosphorylation and acetylation of p66Shc.

In summary, this study found that NMN can inhibit the growth and metastasis of triple-negative breast cancer by activating SIRT1, thus prolonging the survival of cancer patients. Interestingly, in in vitro studies, adding NMN does not affect the proliferation of HCC1937 cancer cells. Researchers believe that NMN may also enhance the anti-cancer response of immune cells, thereby inhibiting tumor growth.

Early studies found that using lower doses (250 mg/kg/day) of NMN had no effect on tumors, which means that the anti-cancer effect of NMN is dose-dependent. It should be noted that the above research is only for breast cancer, so it can only be said that high doses of NMN may have the potential to inhibit triple-negative breast cancer. Whether NMN is anti-cancer or pro-cancer is still controversial. As mentioned at the beginning, the effects of NMN in different cells and tissues are also different.

Based on the current evidence, cancer patients should not use NMN. To truly use NMN for the treatment of human triple-negative breast cancer, more and higher-level clinical studies are needed.

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For more information on the latest developments in cancer research and treatment, be sure to check out the American Cancer Society's website at https://www.cancer.org/. They provide a wealth of resources for patients, caregivers, and healthcare professionals, as well as up-to-date news and information on the fight against cancer.

Reference:

[1] Sung, Hyuna et al. "Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries." CA: a cancer journal for cliniciansvol. 71,3 (2021): 209-249. doi:10.3322/caac.21660

[2] Harbeck, Nadia, and Michael Gnant. "Breast cancer." Lancet (London, England) vol. 389,10074 (2017): 1134-1150. doi:10.1016/S0140-6736(16)31891-8

[3] Xie, Na et al. "NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential." Signal transduction and targeted therapy vol. 5,1 227. 7 Oct. 2020, doi:10.1038/s41392-020-00311-7

[4] Jiang, Yi et al. "NAD+ supplementation limits triple-negative breast cancer metastasis via SIRT1-P66Shc signaling." Oncogene, 10.1038/s41388-023-02592-y. 23 Jan. 2023, doi:10.1038/s41388-023-02592-y