Melatonin impedes prostate cancer metastasis by suppressing MMP‐13 expression

Wang, Shih‐Wei; Tai, Huai‐Ching; Tang, Chih‐Hsin; Lin, Liang-Wei; Lin, Tien‐Huang; Chang, An‐Chen; Chen, Po-Chun; Chen, Yi‐Hsuan; Wang, Po-Chuan; Lai, Yu-Wei; Chen, Shiou-Sheng

doi:10.1002/jcp.30150

Cited by 49 publications

(46 citation statements)

References 44 publications

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“…Melatonin also attenuates endothelial dysfunction in diabetic cardiomyopathy [32]. Furthermore, melatonin inhibits oxidative stress, calcium overload, and inflammation response in endothelial cells under different disease models [33,34]. In the present study, we examined whether ox-LDL-induced endothelial dysfunction is associated with ER stress and JNK/Mff signaling pathway activation.…”

Section: Introductionmentioning

confidence: 94%

Melatonin Attenuates ox‐LDL‐Induced Endothelial Dysfunction by Reducing ER Stress and Inhibiting JNK/Mff Signaling

Xie¹,

Zhong

Guo

et al. 2021

Oxidative Medicine and Cellular Longevity

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Endothelial dysfunction, which is characterized by damage to the endoplasmic reticulum (ER) and mitochondria, is involved in a variety of cardiovascular disorders. Here, we explored whether mitochondrial damage and ER stress are associated with endothelial dysfunction. We also examined whether and how melatonin protects against oxidized low-density lipoprotein- (ox-LDL-) induced damage in endothelial cells. We found that CHOP, GRP78, and PERK expressions, which are indicative of ER stress, increased significantly in response to ox-LDL treatment. ox-LDL also induced mitochondrial dysfunction as evidenced by decreased mitochondrial membrane potential, increased mitochondrial ROS levels, and downregulation of mitochondrial protective factors. In addition, ox-LDL inhibited antioxidative processes, as evidenced by decreased antioxidative enzyme activity and reduced Nrf2/HO-1 expression. Melatonin clearly reduced ER stress and promoted mitochondrial function and antioxidative processes in the presence of ox-LDL. Molecular investigation revealed that ox-LDL activated the JNK/Mff signaling pathway, and melatonin blocked this effect. These results demonstrate that ox-LDL induces ER stress and mitochondrial dysfunction and activates the JNK/Mff signaling pathway, thereby contributing to endothelial dysfunction. Moreover, melatonin inhibited JNK/Mff signaling and sustained ER homeostasis and mitochondrial function, thereby protecting endothelial cells against ox-LDL-induced damage.

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Section: Introductionmentioning

confidence: 94%

Melatonin Attenuates ox‐LDL‐Induced Endothelial Dysfunction by Reducing ER Stress and Inhibiting JNK/Mff Signaling

Xie¹,

Zhong

Guo

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…The imminent need to identify and investigate novel therapeutic approaches in cancer research determines melatonin as a promising agent targeted on cancer combined with conventional therapies. Further investigation on melatonin’s role in cancer initiation and progression can improve its therapeutical potential in the clinical sphere [ 102 , 163 , 164 , 165 ].…”

Section: Expert Recommendations In the Framework Of Predictive Preventive And Personalized (3p) Medicinementioning

confidence: 99%

Metabolic Anti-Cancer Effects of Melatonin: Clinically Relevant Prospects

Samec

Líšková

Koklesová

et al. 2021

Cancers

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Metabolic reprogramming characterized by alterations in nutrient uptake and critical molecular pathways associated with cancer cell metabolism represents a fundamental process of malignant transformation. Melatonin (N-acetyl-5-methoxytryptamine) is a hormone secreted by the pineal gland. Melatonin primarily regulates circadian rhythms but also exerts anti-inflammatory, anti-depressant, antioxidant and anti-tumor activities. Concerning cancer metabolism, melatonin displays significant anticancer effects via the regulation of key components of aerobic glycolysis, gluconeogenesis, the pentose phosphate pathway (PPP) and lipid metabolism. Melatonin treatment affects glucose transporter (GLUT) expression, glucose-6-phosphate dehydrogenase (G6PDH) activity, lactate production and other metabolic contributors. Moreover, melatonin modulates critical players in cancer development, such as HIF-1 and p53. Taken together, melatonin has notable anti-cancer effects at malignancy initiation, progression and metastasing. Further investigations of melatonin impacts relevant for cancer metabolism are expected to create innovative approaches supportive for the effective prevention and targeted therapy of cancers.

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“…Melatonin (N-acetyl-5-methoxytryptamine), an indolamine that is primarily synthesized and secreted by the pineal gland, has various biological functions such as regulation of circadian rhythm, as well as antioxidant, anti-aging, and antitumor activities [ 10 ]. There is a large amount of evidence on the benefits of melatonin in anticancer properties including its pro-apoptotic, anti-proliferative, anti-angiogenic, and anti-metastatic properties [ 11 , 12 , 13 ]. Melatonin also has a synergistic effect with different chemotherapeutic drugs [ 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Melatonin Downregulates PD-L1 Expression and Modulates Tumor Immunity in KRAS-Mutant Non-Small Cell Lung Cancer

Chao

Lee

et al. 2021

IJMS

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Non-small cell lung cancer (NSCLC) patients harboring a KRAS mutation have unfavorable therapeutic outcomes with chemotherapies, and the mutation also renders tolerance to immunotherapies. There is an unmet need for a new strategy for overcoming immunosuppression in KRAS-mutant NSCLC. The recently discovered role of melatonin demonstrates a wide spectrum of anticancer impacts; however, the effect of melatonin on modulating tumor immunity is largely unknown. In the present study, melatonin treatment significantly reduced cell viability accompanied by inducing cell apoptosis in KRAS-mutant NSCLC cell lines including A549, H460, and LLC1 cells. Mechanistically, we found that lung cancer cells harboring the KRAS mutation exhibited a higher level of programmed death ligand 1 (PD-L1). However, treatment with melatonin substantially downregulated PD-L1 expressions in both the presence and absence of interferon (IFN)-γ stimulation. Moreover, KRAS-mutant lung cancer cells exhibited higher Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) levels, and PD-L1 expression was positively correlated with YAP and TAZ in lung cancer cells. Treatment with melatonin effectively suppressed YAP and TAZ, which was accompanied by downregulation of YAP/TAZ downstream gene expressions. The combination of melatonin and an inhibitor of YAP/TAZ robustly decreased YAP and PD-L1 expressions. Clinical analysis using public databases revealed that PD-L1 expression was positively correlated with YAP and TAZ in patients with lung cancer, and PD-L1 overexpression suggested poor survival probability. An animal study further revealed that administration of melatonin significantly inhibited tumor growth and modulated tumor immunity in a syngeneic mouse model. Together, our data revealed a novel antitumor mechanism of melatonin in modulating the immunosuppressive tumor microenvironment by suppressing the YAP/PD-L1 axis and suggest the therapeutic potential of melatonin for treating NSCLC.

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Melatonin impedes prostate cancer metastasis by suppressing MMP‐13 expression

Cited by 49 publications

References 44 publications

Melatonin Attenuates ox‐LDL‐Induced Endothelial Dysfunction by Reducing ER Stress and Inhibiting JNK/Mff Signaling

Melatonin Attenuates ox‐LDL‐Induced Endothelial Dysfunction by Reducing ER Stress and Inhibiting JNK/Mff Signaling

Metabolic Anti-Cancer Effects of Melatonin: Clinically Relevant Prospects

Melatonin Downregulates PD-L1 Expression and Modulates Tumor Immunity in KRAS-Mutant Non-Small Cell Lung Cancer

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