Abstract
Niacin, also known as vitamin B3 or nicotinamide is a water-soluble vitamin that is present in black beans and rice among other foods. Niacin is well known as an inhibitor of metastasis in human breast carcinoma cells but the effect of niacin treatment on TRAIL-mediated apoptosis is unknown. Here, we show that niacin plays an important role in the regulation of autophagic flux and protects tumor cells against TRAIL-mediated apoptosis. Our results indicated that niacin activated autophagic flux in human colon cancer cells and the autophagic flux activation protected tumor cells from TRAIL-induced dysfunction of mitochondrial membrane potential and tumor cell death. We also demonstrated that ATG5 siRNA and autophagy inhibitor blocked the niacin-mediated inhibition of TRAIL-induced apoptosis. Taken together, our study is the first report demonstrating that niacin inhibits TRAIL-induced apoptosis through activation of autophagic flux in human colon cancer cells. And our results also suggest that autophagy inhibitors including genetic and pharmacological tools may be a successful therapeutics during anticancer therapy using TRAIL.
Highlights
Niacin, known as vitamin B3, niacinamide and nicotinamide, is a water-soluble vitamin that humans are unable to synthesize in sufficient amounts [1]
Niacin inhibited Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell death in a dose-dependent manner. The both cell morphology data and crystal violet showed that the combination of TRAIL with niacin decreased the number of apoptotic cells compared with TRAIL alone (Figure 1A and Figure 1B)
Our study suggests that niacin induces autophagic flux in TRAIL-induced apoptosis through down-regulation of death receptors proteins death receptor 4 (DR4) and DR5 and prevention of mitochondria membrane depolarization
Summary
Known as vitamin B3, niacinamide and nicotinamide, is a water-soluble vitamin that humans are unable to synthesize in sufficient amounts [1]. Nicotinamide can block drug-induced apoptosis in human cortical neuronal cells [2]. An absence of niacin causes the deficiency disease pellagra, dementia, diarrhea, and skin problems such as dermatitis [3]. Treatment with niacin has the potential to impair genomic stability and enhances the risk for cancer by regulation of intracellular calcium signaling pathways [4]. Niacin enhances the NAD+/NADH ratio and induces therapeutic normalization of NAD+/NADH balance through autophagy in human breast adenocarcinoma cells [5]. Treatment with niacin activates the PI3K/Akt cascade in the A431 human epithelial carcinoma cell line [6]
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