Induction of Nur77-dependent apoptotic pathway by a coumarin derivative through activation of JNK and p38 MAPK

Zhou, Yuqi; Zhao, Wei; Xie, Guobin; Huang, Ming‐Feng; Hu, Mengjie; Jiang, Xin; Zeng, Deqiang; Liu, Jie; Zhou, Hu; Chen, Haifeng; Wang, Guanghui; Zhang, Xiaokun

doi:10.1093/carcin/bgu186

Cited by 39 publications

(32 citation statements)

References 47 publications

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“…These findings are consistent with those of a previous report [23]. Recent studies have suggested a key role for p38 MAPK and JNK in mediating pathways leading to apoptosis and growth-inhibitory signals [37,38]. Additionally, p38 MAPK and JNK trigger caspase-3 activation and are also necessary for the phosphorylation of apoptosis-related proteins, including Bax and Bcl-2, in cancer cells [23,39].…”

Section: Melatonin Enhances the Effectiveness Of Cisplatin By Suppressupporting

confidence: 93%

Melatonin Induces Cell Apoptosis in AGS Cells Through the Activation of JNK and P38 MAPK and the Suppression of Nuclear Factor-Kappa B: a Novel Therapeutic Implication for Gastric Cancer

Liu

Fan

Chen

et al. 2015

Cell Physiol Biochem

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Background/Aims: Melatonin, synthesized by the pineal gland and released into the blood, appears to have antitumour properties; however, the mechanisms of its anti-cancer effects are largely unknown, especially in stomach cancer. Here, we explore the antitumour activity of melatonin in a gastric cancer cell line (AGS) and analyse its molecular mechanisms. Methods: AGS cells were treated with melatonin, and cell viability was assessed using a CCK-8 assay. Flow cytometry was performed to evaluate apoptosis, and protein expression was examined by Western blotting. Results: Melatonin significantly inhibited cell viability, clone formation, and cell migration and invasion and induced apoptosis in AGS cells. Moreover, MAPK pathways (p38, JNK and ERK) were activated by melatonin treatment, which also significantly increased caspase-3 cleavage and Bax protein expression and decreased Bcl-2 protein expression in a time-dependent manner. Our results demonstrate that p38 and JNK inhibitors (SB203580 and SP600125, respectively) prevented melatonin-induced apoptosis; thus, the propensity of p38 MAPK and JNK to promote apoptosis could be at least partly due to the inhibition of NF-κB p65 activation by p38 and JNK. Finally, melatonin was able to strengthen cisplatin-mediated antitumour effects in human gastric carcinoma cells by up-regulating the expression of Bax, down-regulating the expression of Bcl-2 and activating the caspase-dependent apoptotic pathway. Conclusion: Melatonin induced apoptosis in AGS cells by activating the caspase-dependent apoptotic pathway and by inhibiting the nuclear translocation of NF-κB p65, two processes that are regulated by p38 and JNK. Furthermore, melatonin significantly enhanced the anti-tumour effects of cisplatin, with low systemic toxicity. These new findings suggest that melatonin may act as a potent anti-tumour agent and may have great potential as an adjuvant therapy in the future.

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Section: Melatonin Enhances the Effectiveness Of Cisplatin By Suppressupporting

confidence: 93%

Melatonin Induces Cell Apoptosis in AGS Cells Through the Activation of JNK and P38 MAPK and the Suppression of Nuclear Factor-Kappa B: a Novel Therapeutic Implication for Gastric Cancer

Liu

Fan

Chen

et al. 2015

Cell Physiol Biochem

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“…5). Recent research suggests an important role for JNK and ERK in pathways related to apoptosis and growth-inhibitory pathways (27,28). In addition, JNK induces caspase-3 activation and JNK is necessary for the phosphorylation of proteins related to apoptosis in cancer cells, including Bcl-2 and Bax (29).…”

Section: Discussionmentioning

confidence: 99%

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

Liu

et al. 2016

Oncology Reports

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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.

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“…High level expression of phosphorylated P38 MAPK was detected after TIPE2 up-regulation. Recent studies have suggested a key role for P38 MAPK in mediating pathways leading to apoptosis and growth inhibitory signals [ 23 , 24 ]. Additionally, P38 MAPK triggers the activation of caspase-3, 9 and is also necessary for the phosphorylation of apoptosis-related proteins, including Bax, Bim and Bcl-2 in OA-treated cancer cells [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

TIPE2 Inhibits Lung Cancer Growth Attributing to Promotion of Apoptosis by Regulating Some Apoptotic Molecules Expression

et al. 2015

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Recent studies found that TIPE2 was involved in cancer development. However, little is known about TIPE2 in lung cancer. Our study aims to clarify the role of TIPE2 in lung carcinogenesis. We examined the expression of TIPE2 in lung squamous cancer (LSC), small cell lung cancer and lung adenocarcinoma (AdC) tissues and found that TIPE2 expression was lost in small cell lung cancer, compared with adjacent non-tumor tissues. Overexpression of TIPE2 significantly inhibited the growth of lung cancer cell H446 in vitro and even suppressed tumor formation in vivo. Flow cytometry analysis found TIPE2 overexpression promoted apoptosis of H446. In TIPE2 over-expression cells, caspase-3, caspase-9, and Bax were significantly up-regulated while Bcl-2 was down-regulated. Moreover, coincident results were shown by immunohistochemistry in tumors from nude mice. TIPE2 inhibited the phosphorylation of Akt, while promoting the phosphorylation of P38, but had no effect on IκBα and ERK pathway. Taken together, TIPE2 promoted lung cancer cell apoptosis through affecting apoptosis-related molecules caspase-3, caspase-9, Bcl-2 and Bax, possibly via regulating P38 and Akt pathways, indicating that TIPE2 might be a novel marker for lung cancer diagnosis and therapy.

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Induction of Nur77-dependent apoptotic pathway by a coumarin derivative through activation of JNK and p38 MAPK

Cited by 39 publications

References 47 publications

Melatonin Induces Cell Apoptosis in AGS Cells Through the Activation of JNK and P38 MAPK and the Suppression of Nuclear Factor-Kappa B: a Novel Therapeutic Implication for Gastric Cancer

Melatonin Induces Cell Apoptosis in AGS Cells Through the Activation of JNK and P38 MAPK and the Suppression of Nuclear Factor-Kappa B: a Novel Therapeutic Implication for Gastric Cancer

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

TIPE2 Inhibits Lung Cancer Growth Attributing to Promotion of Apoptosis by Regulating Some Apoptotic Molecules Expression

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