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Article

Dietary Melatonin and Glycine Decrease Tumor Growth through Antiangiogenic Activity in Experimental Colorectal Liver Metastasis

1
General, Visceral and Transplant Surgery, Department of Surgery, Medical University of Graz, Auenbruggerplatz 2, 8036 Graz, Austria
2
Faculty of Medicine, Vilnius University, Ciurlionio 21, 03101 Vilnius, Lithuania
*
Author to whom correspondence should be addressed.
Academic Editor: Anna Kipp
Nutrients 2021, 13(6), 2035; https://doi.org/10.3390/nu13062035
Received: 6 May 2021 / Revised: 7 June 2021 / Accepted: 9 June 2021 / Published: 13 June 2021
Despite multimodal treatment strategies, clinical outcomes of advanced stage colorectal cancer (CRC) patients remain poor. Neoadjuvant/adjuvant chemotherapy efficacy is limited due to 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 combined effects in experimental CRC liver metastases. CRC metastasis with CC531 cells were induced in male Wistar rats. Melatonin and glycine alone or their combination were supplemented for 14 days (n = 100). Blood parameters, a micro-computed tomography scan (tumor volume over time), and immunohistochemistry for Ki67 and CD31 expression in tumor tissue were compared between groups. 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. Most interestingly, the combination therapy did not have any influence on the above-mentioned tumor parameters. The leukocyte count was significantly increased with melatonin at the end of the experiment (p = 0.012) which was due to a high lymphocytes count. Tumor microvascular density was significantly reduced in all treatment groups. The results of this study suggest an inhibitory function for melatonin and glycine alone in the case of CRC liver metastasis growth by acting as natural antiangiogenic molecules, followed by angiogenesis-dependent cancer proliferation and immunomodulation. View Full-Text
Keywords: melatonin; glycine; colorectal cancer; liver metastases; anticancer drug combination melatonin; glycine; colorectal cancer; liver metastases; anticancer drug combination
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MDPI and ACS Style

Kvietkauskas, M.; Zitkute, V.; Leber, B.; Strupas, K.; Stiegler, P.; Schemmer, P. Dietary Melatonin and Glycine Decrease Tumor Growth through Antiangiogenic Activity in Experimental Colorectal Liver Metastasis. Nutrients 2021, 13, 2035. https://doi.org/10.3390/nu13062035

AMA Style

Kvietkauskas M, Zitkute V, Leber B, Strupas K, Stiegler P, Schemmer P. Dietary Melatonin and Glycine Decrease Tumor Growth through Antiangiogenic Activity in Experimental Colorectal Liver Metastasis. Nutrients. 2021; 13(6):2035. https://doi.org/10.3390/nu13062035

Chicago/Turabian Style

Kvietkauskas, Mindaugas, Viktorija Zitkute, Bettina Leber, Kestutis Strupas, Philipp Stiegler, and Peter Schemmer. 2021. "Dietary Melatonin and Glycine Decrease Tumor Growth through Antiangiogenic Activity in Experimental Colorectal Liver Metastasis" Nutrients 13, no. 6: 2035. https://doi.org/10.3390/nu13062035

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