Title Dietary melatonin and glycine decrease tumor growth through antiangiogenic activity in experimental colorectal liver metastasis /
Authors Kvietkauskas, Mindaugas ; Žitkutė, Viktorija ; Leber, Bettina ; Strupas, Kęstutis ; Stiegler, Philipp ; Schemmer, Peter
DOI 10.3390/nu13062035
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Is Part of Nutrients.. Basel : MDPI. 2021, vol. 13, no. 6, art. no. 2035, p. [1-12].. eISSN 2072-6643
Keywords [eng] melatonin ; glycine ; colorectal cancer ; liver metastases ; anticancer drug combination
Abstract [eng] Despite multimodal treatment strategies, clinical outcomes of advanced stage colorectalcancer (CRC) patients remain poor. Neoadjuvant/adjuvant chemotherapy efficacy is limited dueto chemoresistance, toxicity, and negative side effects. Since both melatonin and glycine have anti-cancer activities without relevant side effects, this study was designed to investigate their combinedeffects in experimental CRC liver metastases. CRC metastasis with CC531 cells were induced inmale Wistar rats. Melatonin and glycine alone or their combination were supplemented for14 days(n= 100). Blood parameters, a micro-computed tomography scan (tumor volume over time), andimmunohistochemistry for Ki67 and CD31 expression in tumor tissue were compared betweengroups. Melatonin and glycine alone significantly reduced the tumor volume by 63.2% (p= 0.002)and 43% (p= 0.044) over time, respectively, while tumor volume increased by 8.7% in the controls.Moreover, treatment with melatonin and glycine alone reduced the tumor proliferation index. Mostinterestingly, the combination therapy did not have any influence on the above-mentioned tumorparameters. The leukocyte count was significantly increased with melatonin at the end of theexperiment (p= 0.012) which was due to a high lymphocytes count. Tumor microvascular densitywas significantly reduced in all treatment groups. The results of this study suggest an inhibitoryfunction for melatonin and glycine alone in the case of CRC liver metastasis growth by acting asnatural antiangiogenic molecules, followed by angiogenesis-dependent cancer proliferation andimmunomodulation.
Published Basel : MDPI
Type Journal article
Language English
Publication date 2021
CC license CC license description