Melatonin Regulates Angiogenic and Inflammatory Proteins in MDA-MB-231 Cell Line and in Co-culture with Cancer-associated Fibroblasts

Maschio‐Signorini, Larissa Bazela; Gelaleti, Gabriela Bottaro; Moschetta, Marina Gobbe; Borin, Thaiz F.; Jardim‐Perassi, Bruna V.; Lopes, Jair; Lacerda, Jéssica Zani; Roela, Rosimeire Aparecida; Bordin, Newton Antonio; Corrêa, Lizandra A.; Cardoso, Jessica P.; Zuccari, Débora Aparecida Pires de Campos

doi:10.2174/1871520616666160422105920

Cited by 25 publications

(19 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a study designed to examine vesicle release from normal interstitial cells of the seminal vesicle, melatonin influenced shedding of exosomes (also of ectosomes and multivesicular bodies) leading to changes in paracrine signaling of adjacent cells [376]. Considering the significance of the immune system to tumor cell biology, examining the immune state of both cells and exosomes of the microenvironment of tumor cells would be informative in terms of understanding the role of melatonin in determining tumor progression [377]. …”

Section: Concluding Remarks and Perspectivesmentioning

confidence: 99%

Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis

Reíter

Rosales-Corral

Tan

et al. 2017

IJMS

376

368

View full text Add to dashboard Cite

There is highly credible evidence that melatonin mitigates cancer at the initiation, progression and metastasis phases. In many cases, the molecular mechanisms underpinning these inhibitory actions have been proposed. What is rather perplexing, however, is the large number of processes by which melatonin reportedly restrains cancer development and growth. These diverse actions suggest that what is being observed are merely epiphenomena of an underlying more fundamental action of melatonin that remains to be disclosed. Some of the arresting actions of melatonin on cancer are clearly membrane receptor-mediated while others are membrane receptor-independent and involve direct intracellular actions of this ubiquitously-distributed molecule. While the emphasis of melatonin/cancer research has been on the role of the indoleamine in restraining breast cancer, this is changing quickly with many cancer types having been shown to be susceptible to inhibition by melatonin. There are several facets of this research which could have immediate applications at the clinical level. Many studies have shown that melatonin’s co-administration improves the sensitivity of cancers to inhibition by conventional drugs. Even more important are the findings that melatonin renders cancers previously totally resistant to treatment sensitive to these same therapies. Melatonin also inhibits molecular processes associated with metastasis by limiting the entrance of cancer cells into the vascular system and preventing them from establishing secondary growths at distant sites. This is of particular importance since cancer metastasis often significantly contributes to death of the patient. Another area that deserves additional consideration is related to the capacity of melatonin in reducing the toxic consequences of anti-cancer drugs while increasing their efficacy. Although this information has been available for more than a decade, it has not been adequately exploited at the clinical level. Even if the only beneficial actions of melatonin in cancer patients are its ability to attenuate acute and long-term drug toxicity, melatonin should be used to improve the physical wellbeing of the patients. The experimental findings, however, suggest that the advantages of using melatonin as a co-treatment with conventional cancer therapies would far exceed improvements in the wellbeing of the patients.

show abstract

Section: Concluding Remarks and Perspectivesmentioning

confidence: 99%

Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis

Reíter

Rosales-Corral

Tan

et al. 2017

IJMS

376

368

View full text Add to dashboard Cite

show abstract

“…In addition, we observed the action of melatonin in decreasing vimentin and claudin 7 proteins, and increasing E-cadherin. According to the literature, this molecule regulates the proliferation of mammary tumor cells, angiogenesis-promoting proteins, and reduces breast cancer tumors in xenographic model (37)(38)(39). Melatonin also acts in metastatic control (22) and decreases the ability of tumor cells to invade and migrate (40).…”

Section: Discussionmentioning

confidence: 99%

Melatonin down-regulates microRNA-10a and decreases invasion and migration of triple-negative breast cancer cells

et al. 2019

View full text Add to dashboard Cite

Breast cancer metastasis is one of the main factors associated with high mortality rates among patients. MicroRNAs (miRNAs) play an important role in gene expression regulation, and are associated with the metastatic process in breast cancer. Melatonin, a hormone secreted mainly in the pineal gland, has several oncostatic effects. The aim of this study was to investigate the action of melatonin in the modulation of miRNA-10a-5p and its association with metastatic mechanisms. We have evaluated the effects of melatonin on cell viability in MDA-MB-468 cell line after 24 hours of treatment. MDA-MB-468 and MDA-MB-231 cells were either transfected with inhibitor of miR-10a, or received a scrambled miRNA sequence as a negative control, then these cells were treated with or without melatonin. Gene expression of miR-10a was verified by real-time PCR. Invasion and migration assay using matrigel inserts were performed. The protein expression was analyzed by western blotting to quantify the epithelial-mesenchymal transition (EMT) markers (E-cadherin, claudin 7, and vimentin) and proliferation marker (PIK3CA). Our results showed that melatonin (1 mM) significantly decreased cell viability, and also affected miR-10a expression, which suppressed cell invasion and migration. Melatonin reduced vimentin and claudin 7 protein expressions, and increased E-cadherin. In contrast, inhibition of miR-10a reduced vimentin and did not modulate claudin 7 and E-cadherin. In conclusion, we demonstrated the effectiveness of melatonin in decreasing miR-10a, affecting invasion and migration, and proteins involved with the EMT process, which supports its potential role in the regulation of metastasis.

show abstract

“…Inhibition of expression of vascular endothelial growth factor is a central part of this targeting [105]. Melatonin-promoted inhibition of inflammatory events also plays a role in retarding blood vessel proliferation [106] and melatonin can simultaneously reduce content of angiogenic and inflammatory proteins in a mammary tumor cell line [62]. In hepatocellular carcinoma cells, prazosin, an MT3 receptor antagonist, can strongly upregulate the IL-6 gene, involved in inflammatory events and in promoting angiogenesis [107].…”

Section: Mechanismsmentioning

confidence: 99%

Mechanisms Underlying Tumor Suppressive Properties of Melatonin

Bondy

Campbell

2018

IJMS

View full text Add to dashboard Cite

There is considerable evidence that melatonin may be of use in the prevention and treatment of cancer. This manuscript will review some of the human, animal and cellular studies that provide evidence that melatonin has oncostatic properties. Confirmation that melatonin mitigates pathogenesis of cancer will be described from both direct study of its effects on carcinogenesis, and from indirect findings implicating disruption of the circadian cycle. A distinction is made between the role of melatonin in preventing the initiation of the tumorigenic pathway and the ability of melatonin to retard the progression of cancer. Melatonin appears to slow down the rate of advancement of established tumors and there is evidence that it constitutes a valuable complement to standard pharmacological and radiation treatment modalities. There are instances of the beneficial outcomes in cancer treatment which utilize a range of hormones and vitamins, melatonin being among the constituents of the mix. While these complex blends are empirically promising, they are only briefly mentioned here in view of the confounding influence of a multiplicity of agents studied simultaneously. The last section of this review examines the molecular mechanisms that potentially underlie the oncostatic effects of melatonin. Alterations in gene expression following activation of various transcription factors, are likely to be an important mediating event. These changes in gene activity not only relate to cancer but also to the aging process which underlies the onset of most tumors. In addition, epigenetic events such as modulation of histone acetylation and DNA methylation patterns throughout the lifespan of organisms need to be considered. The antioxidant and immunoregulatory roles of melatonin may also contribute to its cancer modulatory properties. Naturally, these mechanisms overlap and interact extensively. Nevertheless, in the interest of clarity and ease of reading, each is discussed as a separate topic section. The report ends with some general conclusions concerning the clinical value of melatonin which has been rather overlooked and understudied.

show abstract

Melatonin Regulates Angiogenic and Inflammatory Proteins in MDA-MB-231 Cell Line and in Co-culture with Cancer-associated Fibroblasts

Cited by 25 publications

References 0 publications

Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis

Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis

Melatonin down-regulates microRNA-10a and decreases invasion and migration of triple-negative breast cancer cells

Mechanisms Underlying Tumor Suppressive Properties of Melatonin

Contact Info

Product

Resources

About