The Role of Nicotinamide in Cancer Chemoprevention and Therapy

Nikas, Ilias P.; Paschou, Stavroula Α.; Ryu, Han Suk

doi:10.3390/biom10030477

Cited by 73 publications

(63 citation statements)

References 145 publications

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“…Additional studies have shown the anti-melanoma action of sirtuins inhibitors, [ 25 – 27 ], indicating that inhibiting sirtuins may represent an effective way to control melanoma growth [ 28 ]. As recently pointed out, the role played by NAM in melanoma needs further investigation [ 29 ]. NAM is a central player in controlling energy metabolism.…”

Section: Introductionmentioning

confidence: 99%

Nicotinamide inhibits melanoma in vitro and in vivo

Scatozza

Moschella

D’Arcangelo

et al. 2020

J Exp Clin Cancer Res

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Background Even though new therapies are available against melanoma, novel approaches are needed to overcome resistance and high-toxicity issues. In the present study the anti-melanoma activity of Nicotinamide (NAM), the amide form of Niacin, was assessed in vitro and in vivo. Methods Human (A375, SK-MEL-28) and mouse (B16-F10) melanoma cell lines were used for in vitro investigations. Viability, cell-death, cell-cycle distribution, apoptosis, Nicotinamide Adenine Dinucleotide+ (NAD+), Adenosine Triphosphate (ATP), and Reactive Oxygen Species (ROS) levels were measured after NAM treatment. NAM anti-SIRT2 activity was tested in vitro; SIRT2 expression level was investigated by in silico transcriptomic analyses. Melanoma growth in vivo was measured in thirty-five C57BL/6 mice injected subcutaneously with B16-F10 melanoma cells and treated intraperitoneally with NAM. Interferon (IFN)-γ-secreting murine cells were counted with ELISPOT assay. Cytokine/chemokine plasmatic levels were measured by xMAP technology. Niacin receptors expression in human melanoma samples was also investigated by in silico transcriptomic analyses. Results NAM reduced up to 90% melanoma cell number and induced: i) accumulation in G1-phase (40% increase), ii) reduction in S- and G2-phase (about 50% decrease), iii) a 10-fold increase of cell-death and 2.5-fold increase of apoptosis in sub-G1 phase, iv) a significant increase of NAD+, ATP, and ROS levels, v) a strong inhibition of SIRT2 activity in vitro. NAM significantly delayed tumor growth in vivo (p ≤ 0.0005) and improved survival of melanoma-bearing mice (p ≤ 0.0001). About 3-fold increase (p ≤ 0.05) of Interferon-gamma (IFN-γ) producing cells was observed in NAM treated mice. The plasmatic expression levels of 6 cytokines (namely: Interleukin 5 (IL-5), Eotaxin, Interleukin 12 (p40) (IL12(p40)), Interleukin 3 (IL-3), Interleukin 10 (IL-10) and Regulated on Activation Normal T Expressed and Secreted (RANTES) were significantly changed in the blood of NAM treated mice, suggesting a key role of the immune response. The observed inhibitory effect of NAM on SIRT2 enzymatic activity confirmed previous evidence; we show here that SIRT2 expression is significantly increased in melanoma and inversely related to melanoma-patients survival. Finally, we show for the first time that the expression levels of Niacin receptors HCAR2 and HCAR3 is almost abolished in human melanoma samples. Conclusion NAM shows a relevant anti-melanoma activity in vitro and in vivo and is a suitable candidate for further clinical investigations.

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Section: Introductionmentioning

confidence: 99%

Nicotinamide inhibits melanoma in vitro and in vivo

Scatozza

Moschella

D’Arcangelo

et al. 2020

J Exp Clin Cancer Res

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“…There is extensive prior experience with nicotinamide in human trials for conditions other than infections [92][93][94][95][96][97][98] [93,94]. Nicotinamide forms part of certain cancer treatment regimens [93] [94]. The recommended daily dose of nicotinamide is 14-16 mg, and nutritional supplementation dosages are usually below 35 mg per day.…”

Section: Accepted Articlementioning

confidence: 99%

Nicotinamide pathways as the root cause of sepsis – an evolutionary perspective on macrophage energetic shifts

Suchard

Savulescu

2021

The FEBS Journal

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Divergent pathways of macrophage metabolism occur during infection, notably switching between oxidative phosphorylation and aerobic glycolysis (Warburg-like metabolism). Concurrently, macrophages shift between alternate and classical activation. A key enzyme upregulated in alternatively activated macrophages is indoleamine 2,3-dioxygenase, which converts tryptophan to kynurenine for de novo synthesis of nicotinamide. Nicotinamide can be used to replenish cellular NAD + supplies. We hypothesize that an insufficient cellular NAD + supply is the root cause of metabolic shifts in macrophages. We assert that manipulation of nicotinamide pathways may correct deleterious immune responses. We propose evaluation of nicotinamide (Vitamin B3) and analogues, including isoniazid, nicotinamide mononucleotide and nicotinamide riboside, as potential therapy for infectious causes of sepsis, including COVID-19.

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“…Strategies for the skin cancer management include surgery, radiation, chemotherapy and cutting-edge targeted therapies [ 13 , 15 ]. Dacarbazine, temozolomide, paclitaxel, cisplatin and carboplatin are generally used to treat melanoma, whereas vismodegib, sonidegib and cetuximab are used to target basal and squamous cell carcinoma.…”

Section: Introductionmentioning

confidence: 99%

Alternative Options for Skin Cancer Therapy via Regulation of AKT and Related Signaling Pathways

Hwang

Chae

Kwak

et al. 2020

IJMS

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Global environmental pollution has led to human exposure to ultraviolet (UV) radiation due to the damaged ozone layer, thereby increasing the incidence and death rate of skin cancer including both melanoma and non-melanoma. Overexpression and activation of V-akt murine thymoma viral oncogene homolog (AKT, also known as protein kinase B) and related signaling pathways are major factors contributing to many cancers including lung cancer, esophageal squamous cell carcinoma and skin cancer. Although BRAF inhibitors are used to treat melanoma, further options are needed due to treatment resistance and poor efficacy. Depletion of AKT expression and activation, and related signaling cascades by its inhibitors, decreases the growth of skin cancer and metastasis. Here we have focused the effects of AKT and related signaling (PI3K/AKT/mTOR) pathways by regulators derived from plants and suggest the need for efficient treatment in skin cancer therapy.

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The Role of Nicotinamide in Cancer Chemoprevention and Therapy

Cited by 73 publications

References 145 publications

Nicotinamide inhibits melanoma in vitro and in vivo

Nicotinamide inhibits melanoma in vitro and in vivo

Nicotinamide pathways as the root cause of sepsis – an evolutionary perspective on macrophage energetic shifts

Alternative Options for Skin Cancer Therapy via Regulation of AKT and Related Signaling Pathways

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