Melatonin induces cell apoptosis in Mia PaCa-2 cells via the suppression of nuclear factor-κB and activation of ERK and JNK: A novel therapeutic implication for pancreatic cancer

Abstract

Melatonin is synthesized by the pineal gland and is released into the blood. In the last several years, some studies have shown that melatonin has anticancer properties; however, the mechanisms behind the antitumour traits are unclear, especially in pancreatic cancer. Therefore, in the present study, we investigated the antitumour effects of melatonin on the human pancreatic carcinoma cell line MIA PaCa‑2 and explored its biological mechanisms. MIA PaCa‑2 cells were treated with melatonin, and we used a CCK‑8 assay to evaluate the cell viability. We also used flow cytometry to observe cell apoptosis and western blot analysis to assess the protein expression. Our study found that melatonin inhibited cell viability, suppressed colony formation and reduced cell migration and invasion and induced cell apoptosis in MIA PaCa‑2 cells. Our results showed that melatonin treatment inhibited NF‑κB p65 activation. Moreover, melatonin treatment activated the mitogen‑activated protein kinase pathways (c‑jun N‑terminal kinase and extracellular‑regulated kinase 1/2), which increased Bax protein expression and caspase‑3 cleavage and decreased Bcl‑2 protein expression. These new developments demonstrate that melatonin plays a potential role in anticancer treatment and may act as an effective therapeutic agent in the future.

Melatonin inhibits epithelial‑to‑mesenchymal transition in gastric cancer cells via attenuation of IL‑1β/NF‑κB/MMP2/MMP9 signaling

“…NF-κB induces the expression of Snail (20), ZEB-1 and ZEB2 (21) to promote EMT and cancer metastasis. It was also previously demonstrated that melatonin potently inhibits the activity of NF-κB (22). In the present study, EMSA analysis confirmed that IL-1β enhanced NF-κB transcriptional activity.…”

“…It has been reported that NF-κB inhibits the expression of E-cadherin and desmoplakin and induces the expression of vimentin by promoting the expression of Snail (20), ZEB-1 and ZEB-2 (21), thereby initiating EMT. Other studies have demonstrated that melatonin exerts an inhibitory effect on NF-κB (22). However, to the best of our knowledge, there is currently no study investiagting these pathways in Gc.…”

Effects of Melatonin and Its Analogues on Pancreatic Inflammation, Enzyme Secretion, and Tumorigenesis

“…However, the activation of executor of apoptosis (caspase-3) and DNA fragmentation have not been observed, indicating that the apoptotic process might not be completed [43,87,88]. The pro-apoptotic effect of melatonin on pancreatic tumor cells has been demonstrated by Li et al and Xu et al, who have shown that the application of melatonin to cancer cells resulted in the strong expression of pro-apoptotic Bax proteins followed by the activation of caspase-3 and inhibition of an anti-apoptotic protein Bcl-2 [82,89]. Similar results have been demonstrated in the pancreatic AR42J tumor acinar cells.…”

“…According to the data of Li et al [89], melatonin inhibited cell viability, suppressed colony formation, reduced cell migration and invasion, and induced cell apoptosis in pancreatic carcinoma cells. In addition, recent studies have shown that high doses (mM) of melatonin decreased pancreatic tumor cells proliferation and invasion by inhibition of NF-κB signaling pathway, but also enhanced gemcitabine cytotoxicity in these cells [100].…”

Beneficial effects of melatonin in juvenile rats with heart failure

“…Plenty of studies have shown that melatonin and its metabolites can serve as broad-spectrum antioxidants and free radical scavengers [26][27][28] . They can potentially regulate the process of apoptosis and inflammation in cardiovascular diseases.…”