Melatonin as an angiogenesis inhibitor to combat cancer: Mechanistic evidence

Goradel, Nasser Hashemi; Asghari, Mohammad Hossein; Moloudizargari, Milad; Negahdari, Babak; Haghi‐Aminjan, Hamed; Abdollahi, Mohammad

doi:10.1016/j.taap.2017.09.022

Cited by 91 publications

(69 citation statements)

References 74 publications

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“…Metastasis of CRC is a complex progress in which angiogenesis has been reported as an essential step 36 . Restraining tumor-associated angiogenesis has been shown to be a promising tactic in preventing cancer progression and metastasis 37 , 38 . Several members of the KIF family have been reported to be involved in the regulation of angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

KIF4A facilitates cell proliferation via induction of p21-mediated cell cycle progression and promotes metastasis in colorectal cancer

et al. 2018

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Kinesin family member 4A (KIF4A) was found to be implicated in the regulation of chromosome condensation and segregation during mitotic cell division, which is essential for eukaryotic cell proliferation. However, little is known about the role of KIF4A in colorectal carcinoma (CRC). This study explored the biological function of KIF4A in CRC progression and investigated the potential molecular mechanisms involved. Here, we found that KIF4A was remarkably upregulated in primary CRC tissues and cell lines compared with paired non-cancerous tissues and normal colorectal epithelium. Elevated expression of KIF4A in CRC tissues was significantly correlated with clinicopathological characteristics in patients as well as with shorter overall and disease-free cumulative survival. Multivariate Cox regression analysis revealed that KIF4A was an independent prognostic factor for poor survival in human CRC patients. Functional assays, including a CCK-8 cell proliferation assay, colony formation analysis, cancer xenografts in nude mice, cell cycle and apoptosis analysis, indicated that KIF4A obviously enhanced cell proliferation by promoting cell cycle progression in vitro and in vivo. Furthermore, gene set enrichment analysis, Luciferase reporter assays, and ChIP assays revealed that KIF4A facilitates cell proliferation via regulating the p21 promoter, whereas KIF4A had no effect on cell apoptosis. In addition, Transwell analysis indicated that KIF4A promotes migration and invasion in CRC. Taken together, these findings not only demonstrate that KIF4A contributes to CRC proliferation via modulation of p21-mediated cell cycle progression but also suggest the potential value of KIF4A as a clinical prognostic marker and target for molecular treatments.

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Section: Discussionmentioning

confidence: 99%

KIF4A facilitates cell proliferation via induction of p21-mediated cell cycle progression and promotes metastasis in colorectal cancer

et al. 2018

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“…This hormone also regulates angiogenesis under hypoxia in MCF-7 and MDA-MB-231 cells [29] and decreases the expression of genes related to this process in MDA-MB-231 and MCF-7 cells in three-dimensional culture [30]. Thus, genes related to angiogenesis can be regulated by various mechanisms and molecules, including miRNAs [31] and melatonin [32].…”

Section: Discussionmentioning

confidence: 99%

Melatonin restrains angiogenic factors in triple-negative breast cancer by targeting miR-152-3p: In vivo and in vitro studies

et al. 2018

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“…The mechanisms underlying this are manifold but ultimately lead to a reduction of expression levels of genes required for angiogenesis [104]. Inhibition of expression of vascular endothelial growth factor is a central part of this targeting [105].…”

Section: Mechanismsmentioning

confidence: 99%

Mechanisms Underlying Tumor Suppressive Properties of Melatonin

Bondy

Campbell

2018

IJMS

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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.

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Melatonin as an angiogenesis inhibitor to combat cancer: Mechanistic evidence

Cited by 91 publications

References 74 publications

KIF4A facilitates cell proliferation via induction of p21-mediated cell cycle progression and promotes metastasis in colorectal cancer

KIF4A facilitates cell proliferation via induction of p21-mediated cell cycle progression and promotes metastasis in colorectal cancer

Melatonin restrains angiogenic factors in triple-negative breast cancer by targeting miR-152-3p: In vivo and in vitro studies

Mechanisms Underlying Tumor Suppressive Properties of Melatonin

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