Effect of Melatonin in Epithelial Mesenchymal Transition Markers and Invasive Properties of Breast Cancer Stem Cells of Canine and Human Cell Lines

Gonçalves, Naiane do Nascimento; Colombo, Jucimara; Lopes, Jair; Gelaleti, Gabriela Bottaro; Moschetta, Marina Gobbe; Sonehara, Nathália Martins; Hellmén, Eva; Zanon, Caroline de Freitas; Oliani, Sônia Maria; Zuccari, Débora Aparecida Pires de Campos

doi:10.1371/journal.pone.0150407

Cited by 71 publications

(57 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Melatonin (i.e., N ‐acetyl‐5‐methoxytryptamine), a molecule present in all organisms, is synthesized from the amino acid tryptophan in the pineal gland in animals . The role of melatonin in carcinogenic processes is being increasingly clarified; for instance, melatonin induces apoptosis in cancer cells, stimulates antioxidative enzyme expression, suppresses angiogenesis by inhibiting epidermal growth factor and vascular growth factor activities, and inhibits cell metastasis by regulating MMP‐9 expression and EMT . A recent study showed that disruption of the normal circadian melatonin signal promotes the cell growth and metabolism of breast cancer and induces chemotherapeutic resistance .…”

Section: Introductionmentioning

confidence: 99%

Melatonin suppresses TPA‐induced metastasis by downregulating matrix metalloproteinase‐9 expression through JNK/SP‐1 signaling in nasopharyngeal carcinoma

Lin

Chien

et al. 2016

Journal of Pineal Research

102

View full text Add to dashboard Cite

Nasopharyngeal carcinoma (NPC), a disease common in the South-East Asian population, has high lymph node metastatic ability. Melatonin, an endogenously produced substance present in animals, plants, fungi, and bacteria, has oncostatic activity via several mechanisms. The molecular mechanisms involved in melatonin-mediated tumor inhibitory potential are not completely defined. Here, we show that melatonin treatment inhibits TPA-induced cell motility by regulating the matrix metalloproteinase-9 (MMP-9) expression in NPC. We also identified the signaling cascade through which melatonin inhibits MMP-9 expression; this involves melatonin regulating the binding activity of the transcription factor specificity protein-1 (SP-1)-DNA. Our mechanistic analysis further reveals that the c-Jun N-terminal kinase/mitogen-activated protein kinase pathway is involved in the melatonin-mediated tumor suppressor activity. Furthermore, the findings indicate a functional link between melatonin-mediated MMP-9 regulation and tumor suppressing ability and provide new insights into the role of melatonin-induced molecular and epigenetic regulation of tumor growth. Thus, we conclude that melatonin suppresses the motility of NPC by regulating TPA-induced MMP-9 gene expression via inhibiting SP-1-DNA binding ability. The results provide a functional link between melatonin-mediated SP-1 regulation and the antimetastatic actions of melatonin on nasopharyngeal carcinoma.

show abstract

Section: Introductionmentioning

confidence: 99%

Melatonin suppresses TPA‐induced metastasis by downregulating matrix metalloproteinase‐9 expression through JNK/SP‐1 signaling in nasopharyngeal carcinoma

Lin

Chien

et al. 2016

Journal of Pineal Research

102

View full text Add to dashboard Cite

show abstract

“…Studies have shown that melatonin has the potential of being used as a therapeutic agent for treating various types of human cancer, such as breast cancer , colon cancer , ovarian cancer , prostate cancer and lung cancer . Melatonin exhibits various pharmacological effects against cancer, including suppression of the expression of matrix metalloproteinases and inhibition of invasion and metastasis of cancer cells . Melatonin suppresses MMP‐9 transcription via modulating the expression of CREB‐binding protein (CREBBP) and E1A‐binding protein p300 (EP300), and decreasing histone acetylation , suggesting that histone acetylation plays important roles in melatonin‐related cancer treatment.…”

mentioning

confidence: 99%

Evaluation of cell death pathways initiated by antitumor drugs melatonin and valproic acid in bladder cancer cells

et al. 2017

View full text Add to dashboard Cite

Effective drug combinations have the potential to strengthen therapeutic efficacy and combat drug resistance. Both melatonin and valproic acid ( VPA ) exhibit antitumor activities in various cancer cells. The aim of this study was to evaluate the cell death pathways initiated by anticancer combinatorial effects of melatonin and VPA in bladder cancer cells. The results demonstrated that the combination of melatonin and VPA leads to significant synergistic growth inhibition of UC 3 bladder cancer cells. Gene expression studies revealed that cotreatment with melatonin and VPA triggered the up‐regulation of certain genes related to apoptosis ( TNFRSF 10A and TNFRSF 10B), autophagy ( BECN , ATG 3 and ATG 5) and necrosis ( MLKL , PARP ‐1 and RIPK 1). The combinatorial treatment increased the expression of endoplasmic reticulum ( ER )‐stress‐related genes ATF 6, IRE 1, EDEM 1 and ER dj4. Cotreatment with melatonin and VPA enhanced the expression of E‐cadherin, and decreased the expression of N ‐cadherin, Fibronectin, Snail and Slug. Furthermore, the Wnt pathway and Raf/ MEK / ERK pathway were activated by combinatorial treatment. However, the effects on the expression of certain genes were not further enhanced in cells following combinatorial treatment in comparison to individual treatment of melatonin or VPA . In summary, these findings provided evidence that cotreatment with melatonin and VPA exerted increased cytotoxicity by regulating cell death pathways in UC 3 bladder cancer cells, but the clinical significance of combinatorial treatment still needs to be further exploited.

show abstract

“…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

Self Cite

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

Effect of Melatonin in Epithelial Mesenchymal Transition Markers and Invasive Properties of Breast Cancer Stem Cells of Canine and Human Cell Lines

Cited by 71 publications

References 75 publications

Melatonin suppresses TPA‐induced metastasis by downregulating matrix metalloproteinase‐9 expression through JNK/SP‐1 signaling in nasopharyngeal carcinoma

Melatonin suppresses TPA‐induced metastasis by downregulating matrix metalloproteinase‐9 expression through JNK/SP‐1 signaling in nasopharyngeal carcinoma

Evaluation of cell death pathways initiated by antitumor drugs melatonin and valproic acid in bladder cancer cells

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

Contact Info

Product

Resources

About