Mitochondrial functions and melatonin: a tour of the reproductive cancers

Chuffa, Luiz Gustavo de Almeida; Seiva, Fábio Rodrigues Ferreira; Cucielo, Maira Smaniotto; Silveira, Henrique Spaulonci; Reíter, Russel J.; Lupi, Luiz Antônio

doi:10.1007/s00018-018-2963-0

Cited by 48 publications

(33 citation statements)

References 291 publications

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“…The morphology of mitochondria is dynamically regulated by the balance between fusion and fission events to maintain energy and metabolic homeostasis [12]. During recent years, a series of studies have revealed the close links between mitochondrial dynamic imbalance and various human cancers [15], including liver [16,17], breast [18,19], lung [20,21], colon [22] and ovarian [23,24,33] cancers. MIEF2 (mitochondrial elongation factor 2) is an outer mitochondrial membrane protein involved in the regulation of mitochondrial fission [25].…”

Section: Discussionmentioning

confidence: 99%

MIEF2 over-expression promotes tumor growth and metastasis through reprogramming of glucose metabolism in ovarian cancer

Zhao

Zhang

Shi

et al. 2020

J Exp Clin Cancer Res

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Background Increasing evidence has revealed the close link between mitochondrial dynamic dysfunction and cancer. MIEF2 (mitochondrial elongation factor 2) is mitochondrial outer membrane protein that functions in the regulation of mitochondrial fission. However, the expression, clinical significance and biological functions of MIEF2 are still largely unclear in human cancers, especially in ovarian cancer (OC). Methods The expression and clinical significance of MIEF2 were determined by qRT-PCR, western blot and immunohistochemistry analyses in tissues and cell lines of OC. The biological functions of MIEF2 in OC were determined by in vitro and in vivo cell growth and metastasis assays. Furthermore, the effect of MIEF2 on metabolic reprogramming of OC was determined by metabolomics and glucose metabolism analyses. Results MIEF2 expression was significantly increased in OC mainly due to the down-regulation of miR-424-5p, which predicts poor survival for patients with OC. Knockdown of MIEF2 significantly suppressed OC cell growth and metastasis both in vitro and in vivo by inhibiting G1-S cell transition, epithelial-to-mesenchymal transition (EMT) and inducing cell apoptosis, while forced expression of MIEF2 had the opposite effects. Mechanistically, mitochondrial fragmentation-suppressed cristae formation and thus glucose metabolism switch from oxidative phosphorylation to glycolysis was found to be involved in the promotion of growth and metastasis by MIEF2 in OC cells. Conclusions MIEF2 plays a critical role in the progression of OC and may serve as a valuable prognostic biomarker and therapeutic target in the treatment of this malignancy.

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Section: Discussionmentioning

confidence: 99%

MIEF2 over-expression promotes tumor growth and metastasis through reprogramming of glucose metabolism in ovarian cancer

Zhao

Zhang

Shi

et al. 2020

J Exp Clin Cancer Res

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“…Melatonin is produced and secreted by the pineal gland, and modulates several biological pathways in cancer [105]. Interestingly, GLUT1 appears to be involved in the uptake of melatonin into cancer cells and melatonin appears to bind the glucose binding site of the transporter [106].…”

Section: Melatoninmentioning

confidence: 99%

Targeting Glucose Transporters for Breast Cancer Therapy: The Effect of Natural and Synthetic Compounds

Barbosa

Martel

2020

Cancers

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Reprogramming of cellular energy metabolism is widely accepted to be a cancer hallmark. The deviant energetic metabolism of cancer cells-known as the Warburg effect-consists in much higher rates of glucose uptake and glycolytic oxidation coupled with the production of lactic acid, even in the presence of oxygen. Consequently, cancer cells have higher glucose needs and thus display a higher sensitivity to glucose deprivation-induced death than normal cells. So, inhibitors of glucose uptake are potential therapeutic targets in cancer. Breast cancer is the most commonly diagnosed cancer and a leading cause of cancer death in women worldwide. Overexpression of facilitative glucose transporters (GLUT), mainly GLUT1, in breast cancer cells is firmly established, and the consequences of GLUT inhibition and/or knockout are under investigation. Herein we review the compounds, both of natural and synthetic origin, found to interfere with uptake of glucose by breast cancer cells, and the consequences of interference with that mechanism on breast cancer cell biology. We will also present data where the interaction with GLUT is exploited in order to increase the efficiency or selectivity of anticancer agents, in breast cancer cells.

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“…Melatonin (N‐acetyl‐5‐methoxytryptamine), an indoleamine produced by the pineal gland, has been proven to possess extensive biological activities including circadian rhythms regulation, anti‐oxidation, anti‐inflammation, and neuromodulation . Interestingly, emerging studies suggested that melatonin also exerted anticancer activities against a variety of cancers, such as lung cancer, breast cancer, ovarian cancer, colon cancer . Moreover, melatonin is a well‐known molecule with favorable compatibility and lack of toxicity.…”

Section: Introductionmentioning

confidence: 99%

Histone deacetylase 9 downregulation decreases tumor growth and promotes apoptosis in non‐small cell lung cancer after melatonin treatment

Liu

et al. 2019

Journal of Pineal Research

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Histone deacetylase 9 functions as an oncogene in a variety of cancers, but its role on non-small cell lung cancer (NSCLC) has not been reported. Melatonin was proven to possess anticancer actions, whereas its effect on NSCLC and underlying mechanisms remains poorly understood. In this study, 337 patients with complete clinicopathologic characteristics who underwent NSCLC surgery were recruited for the study. We found that NSCLC patients with high HDAC9 expression were correlated with worse overall survival and poor prognosis. HDAC9 knockdown significantly reduced NSCLC cell growth and induced apoptosis both in vivo and in vitro. Melatonin application also markedly inhibited cell proliferation, metastasis, and invasion and promoted apoptosis in NSCLC cells. Moreover, RNA-seq, real-time quantitative polymerase chain reaction, and western blot analyses showed that melatonin treatment decreased the HDAC9 level in NSCLC cells. A mechanistic study revealed that HDAC9 knockdown further enhanced the anticancer activities of melatonin treatment, whereas HDAC9 overexpression partially reversed the melatonin's anticancer effects. Additionally, the in vivo study found melatonin exerted anti-proliferative and pro-apoptotic effects on xenograft tumors which were also strengthened by HDAC9 knockdown. These results indicated that HDAC9 downregulation mediated the anti-NSCLC actions of melatonin, and targeting HDAC9 may be the novel therapeutic strategy for NSCLC. K E Y W O R D Sapoptosis, HDAC9, melatonin, NSCLC, prognosis, proliferation 2 of 15 | MA et Al.

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Mitochondrial functions and melatonin: a tour of the reproductive cancers

Cited by 48 publications

References 291 publications

MIEF2 over-expression promotes tumor growth and metastasis through reprogramming of glucose metabolism in ovarian cancer

MIEF2 over-expression promotes tumor growth and metastasis through reprogramming of glucose metabolism in ovarian cancer

Targeting Glucose Transporters for Breast Cancer Therapy: The Effect of Natural and Synthetic Compounds

Histone deacetylase 9 downregulation decreases tumor growth and promotes apoptosis in non‐small cell lung cancer after melatonin treatment

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