Melatonin protects against arsenic trioxide-induced liver injury by the upregulation of Nrf2 expression through the activation of PI3K/AKT pathway

Zhang, Yue; Wei, Zhengkai; Liu, Weijian; Wang, Jingjing; He, Xuexiu; Huang, Hailong; Zhang, Jiali; Yang, Zhengtao

doi:10.18632/oncotarget.13931

Cited by 55 publications

(31 citation statements)

References 20 publications

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“…The Akt pathway was affected quite differently in the diverse cell lines: p-Akt increased in DX3 cells, remained unaffected in WM-115 cells, while it dramatically decreased in breast cancer cell lines. Actually, melatonin was previously shown to inhibit Akt phosphorylation in MCF-7 [ 29 ] and MDA-MB231 cells [ 28 ]; though it was recently observed that melatonin could upregulate the PI3K/Akt pathway in other model systems [ 40 , 41 ], including a melanoma cell line [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Antiproliferative and pro-apoptotic activity of melatonin analogues on melanoma and breast cancer cells

et al. 2017

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Melatonin plays different physiological functions ranging from the regulation of circadian rhythms to tumor inhibition, owing to its antioxidant, immunomodulatory and anti-aging properties. Due to its pleiotropic functions, melatonin has been shown to elicit cytoprotective processes in normal cells and trigger pro-apoptotic signals in cancer cells. The therapeutic potential of melatonin analogues prompted us to investigate the in vitro and in vivo antitumor activity of new melatonin derivatives and explore the underlying molecular mechanisms. The experiments revealed that the new melatonin analogues inhibited the growth of melanoma and breast cancer cells in a dose- and time-dependent manner. In addition, our results indicated that melatonin derivative UCM 1037 could induce apoptosis in melanoma and breast cancer cells, as well as cell necrosis, in MCF-7. Together, apoptosis and necrosis could be two possible mechanisms to explain the cytotoxic effect of the melatonin analogue against cancer cells. The suppression of tumor growth by the melatonin analogues was further demonstrated in vivo in a xenograft mice model. A decrease in the activation of MAPK pathway was observed in all cancer cells following UCM 1037 treatment. Overall, this study describes a promising antitumor compound showing antiproliferative and cytotoxic activity in melanoma and breast cancer cells.

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Section: Discussionmentioning

confidence: 99%

Antiproliferative and pro-apoptotic activity of melatonin analogues on melanoma and breast cancer cells

et al. 2017

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“…The consequence of Akt activation is the upregulation of peroxisome proliferator‐activated receptor gamma coactivator 1α (PGC‐1α) followed by upregulated Sirt3 expression and activity . Akt activation is then followed by the improvement of Nrf2 and HO‐1, which is associated with the elevated antioxidant enzymes SOD and GPX . Moreover, Akt activation by melatonin also retards ER stress via targeting GSK‐3β and VDAC .…”

Section: Target Of Melatonin In Cardioprotection Under Ir Injurymentioning

confidence: 99%

Protective role of melatonin in cardiac ischemia‐reperfusion injury: From pathogenesis to targeted therapy

Zhou

Zhu

et al. 2018

Journal of Pineal Research

203

133

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Acute myocardial infarction (MI) is a major cause of mortality and disability worldwide. In patients with MI, the treatment option for reducing acute myocardial ischemic injury and limiting MI size is timely and effective myocardial reperfusion using either thombolytic therapy or primary percutaneous coronary intervention (PCI). However, the procedure of reperfusion itself induces cardiomyocyte death, known as myocardial reperfusion injury, for which there is still no effective therapy. Recent evidence has depicted a promising role of melatonin, which possesses powerful antioxidative and anti‐inflammatory properties, in the prevention of ischemia‐reperfusion (IR) injury and the protection against cardiomyocyte death. A number of reports explored the mechanism of action behind melatonin‐induced beneficial effects against myocardial IR injury. In this review, we summarize the research progress related to IR injury and discuss the unique actions of melatonin as a protective agent. Furthermore, the possible mechanisms responsible for the myocardial benefits of melatonin against reperfusion injury are listed with the prospect of the use of melatonin in clinical application.

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“…According to Wu Set al, HBSP inhibits hepatocyte apoptosis through PI3K/Akt pathway, suggesting that the intervention of inhibiting Akt activation or functional activity may have therapeutic value during the process. PI3K/Akt pathway was reported to be involved in tissue injuries, such as I/R‐induced renal injury, streptozotocin‐induced testicular injury and trioxide‐induced liver injury . Therefore, it is of great significance to take effective measures to regulate PI3K/Akt pathway at the molecular level in the treatment of these diseases.…”

Section: Discussionmentioning

confidence: 99%

Helix B surface peptide reduces sepsis‐induced kidney injury via PI3K/Akt pathway

Sun

Song

et al. 2020

Nephrology

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Aim Helix B‐Surface peptide (HBSP) is the latest discovered erythropoietin (EPO) analogue that can retain the activity of EPO. EPO, which is widely used for treating renal anemia, has recently been proved to have protective effects on ischemia‐reperfusion injury of brain, heart and kidney. The protective effects of EPO and HBSP on cardiac function were found in rats with myocardial ischemia. However, the effect of HBSP on sepsis‐induced renal injury is still unclear. Methods Establishment of rat kidney injury model and treated with HBSP and lipoposaccharide. Renal injury in rats was observed by hematoxylin‐eosin staining and injury index score. Levels of serum creatinine (SCr), blood urea nitrogen (BUN) and Cystatin C (Cys C) were detected using fully automatic biochemical analyzer, tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), and IL‐1β were detected by enzyme‐linked immunosorbent assay. Western blot analysis was performed to determine the role of HBSP in phosphatidylinositol 3‐kinase (PI3K)/Akt pathway. Results Acute kidney injury (AKI) appeared after modeling, however, HBSP alleviated the pathological conditions of the kidney injury. In addition, HBSP lowered kidney injury index score in the rats, and decreased the levels of SCr, BUN, Cys C, TNF‐α, IL‐6 and IL‐1β, moreover, HBSP also showed the effect of activating PI3K/Akt pathway. Conclusion HBSP alleviated lipoposaccharide‐induced AKI and improved kidney function of the rats with sepsis. More importantly, the effects of HBSP on lipoposaccharid‐induced AKI were realized via activating PI3K/Akt pathway. The findings in the current study provide new insights into the therapeutic mechanism for treating the disease.

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Melatonin protects against arsenic trioxide-induced liver injury by the upregulation of Nrf2 expression through the activation of PI3K/AKT pathway

Cited by 55 publications

References 20 publications

Antiproliferative and pro-apoptotic activity of melatonin analogues on melanoma and breast cancer cells

Antiproliferative and pro-apoptotic activity of melatonin analogues on melanoma and breast cancer cells

Protective role of melatonin in cardiac ischemia‐reperfusion injury: From pathogenesis to targeted therapy

Helix B surface peptide reduces sepsis‐induced kidney injury via PI3K/Akt pathway

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