Journal ArticleDOI
Melatonin and associated signaling pathways that control normal breast epithelium and breast cancer.
Steven M. Hill,David E. Blask,Shulin Xiang,Lin Yuan,Lulu Mao,Robert T. Dauchy,Erin M. Dauchy,Tripp Frasch,Tamika Duplesis +8 more
TLDR
Light-at-night (LAN) induced circadian disruption of the nocturnal melatonin signal activates human breast cancer growth, metabolism, and signaling, providing the strongest mechanistic support, thus far, for epidemiological studies demonstrating the elevated breast cancer risk in night shift workers and other individuals increasingly exposed to LAN.Abstract:
This review article discusses recent work on the melatonin-mediated circadian regulation and integration of molecular and metabolic signaling mechanisms involved in human breast cancer growth and the associated consequences of circadian disruption by exposure to light-at-night (LAN). The anti-proliferative effects of the circadian melatonin signal are, in general, mediated through mechanisms involving the activation of MT1 melatonin receptors expressed in human breast cancer cell lines and xenografts. In estrogen receptor-positive (ERα+) human breast cancer cells, melatonin suppresses both ERα mRNA expression and estrogen-induced transcriptional activity of the ERα via MT1-induced activation of Gαi2 signaling and reduction of cAMP levels. Melatonin also regulates the transcriptional activity of additional members of the nuclear receptor super-family, enzymes involved in estrogen metabolism, and the expression of core clock and clock-related genes. The anti-invasive/anti-metastatic actions of melatonin involve the blockade of p38 phosphorylation and matrix metalloproteinase expression. Melatonin also inhibits the growth of human breast cancer xenografts via MT1-mediated suppression of cAMP leading to a blockade of linoleic acid (LA) uptake and its metabolism to the mitogenic signaling molecule 13-hydroxyoctadecadienoic acid (13-HODE). Down-regulation of 13-HODE reduces the activation of growth factor pathways supporting cell proliferation and survival. Finally, studies in both rats and humans indicate that light-at-night (LAN) induced circadian disruption of the nocturnal melatonin signal activates human breast cancer growth, metabolism, and signaling, providing the strongest mechanistic support, thus far, for epidemiological studies demonstrating the elevated breast cancer risk in night shift workers and other individuals increasingly exposed to LAN.read more
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Journal ArticleDOI
Broad targeting of angiogenesis for cancer prevention and therapy
Zongwei Wang,Charlotta Dabrosin,Xin Yin,Mark M. Fuster,Alexandra Arreola,W. Kimryn Rathmell,Daniele Generali,Ganji Purnachandra Nagaraju,Bassel F. El-Rayes,Domenico Ribatti,Yi Charlie Chen,Kanya Honoki,Hiromasa Fujii,Alexandros G. Georgakilas,Somaira Nowsheen,Amedeo Amedei,Elena Niccolai,Amr Amin,S. Salman Ashraf,Bill Helferich,Xujuan Yang,Gunjan Guha,Dipita Bhakta,Maria Rosa Ciriolo,Katia Aquilano,Sophie Chen,Dorota Halicka,Sulma I. Mohammed,Asfar S. Azmi,Alan Bilsland,W. Nicol Keith,Lasse Jensen,Lasse Jensen +32 more
TL;DR: 10 important aspects of tumor angiogenesis and the pathological tumor vasculature which would be well suited as targets for anti-angiogenic therapy are identified and 10 plant-derived compounds could be combined to constitute a broader acting and more effective inhibitory cocktail at doses that would not be likely to cause excessive toxicity.
Journal ArticleDOI
Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis.
Russel J. Reiter,Sergio Rosales-Corral,Dun Xian Tan,Darío Acuña-Castroviejo,Lilan Qin,Shun-Fa Yang,Kexin Xu +6 more
TL;DR: The experimental findings 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.
Journal ArticleDOI
Melatonin: an inhibitor of breast cancer
Steven M. Hill,Victoria P. Belancio,Robert T. Dauchy,Shulin Xiang,Samantha Brimer,Lulu Mao,Adam Hauch,Peter W. Lundberg,Whitney Summers,Lin Yuan,Tripp Frasch,David E. Blask +11 more
TL;DR: Research in animal and human models has indicated that LEN-induced disruption of the circadian nocturnal melatonin signal promotes the growth, metabolism, and signaling of human breast cancer and drives breast tumors to endocrine and chemotherapeutic resistance.
Journal ArticleDOI
Circadian molecular clocks and cancer
TL;DR: Theoretically the cell cycle and malignant disease may be targeted vicariously by selective alteration of the cellular molecular clock.
Journal ArticleDOI
Effect of melatonin on tumor growth and angiogenesis in xenograft model of breast cancer.
Bruna Victorasso Jardim-Perassi,Ali S. Arbab,Lívia Carvalho Ferreira,Thaiz F. Borin,Nadimpalli Ravi S. Varma,A. S. M. Iskander,Adarsh Shankar,Meser M. Ali,Debora Aparecida Pires de Campos Zuccari +8 more
TL;DR: Melatonin treatment showed effectiveness in reducing tumor growth and cell proliferation, as well as in the inhibition of angiogenesis in breast cancer.
References
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