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Gewählte Publikation:

Kvietkauskas, M.
The role of melatonin and glycine in colorectal cancer liver metastases treatment
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Medizinische Universität Graz; 2022. pp. 78 [OPEN ACCESS]


Autor*innen der Med Uni Graz:
Leber Bettina
Schemmer Peter
Stiegler Philipp

Background: Despite multidisciplinary approach, treatment outcomes of patients with advanced stage colorectal cancer are relatively low. Neoadjuvant/adjuvant chemotherapy efficacy is mainly limited due to chemoresistance, toxicity and negative side effects. Recently, melatonin and glycine have been shown to possess anticancer and organoprotective activities. We aimed to investigate the effects of dietary melatonin and glycine supplementation for colorectal cancer liver metastases (CRLM) treatment in a rat model. Materials and Methods: This study was conducted on 180 male Wistar rats with induced CRLM (by implanting rat colon adenocarcinoma cell line CC531 cells) treated with melatonin ± glycine ± FOLFOX chemotherapy for 14 days. Various blood parameters, computed tomography scan (tumour volume over time), heart ultrasound (left ventricular ejection fraction over time), anti-Ki67, and anti-CD31 expression in tumour tissue were analysed and compared between groups. Results: Melatonin and glycine supplementation alone significantly reduced the tumour volume by 63.2 % (p = 0.002) and 43 % (p = 0.044) over time, respectively, while in the control group tumour volume increased by 8.7 %. Treatment with melatonin, glycine, and their combination significantly reduced microvascular density in tumour tissue (p < 0.001, p = 0.018, and p = 0.003, respectively), while tumour proliferation index was significantly reduced only after supplementation with melatonin and glycine alone (p = 0.005 and p = 0.044, respectively) compared to controls. The leukocyte count at the end of experiment was significantly increased (p = 0.012) in the melatonin supplemented group and this was associated with a higher count of lymphocytes (p < 0.001) compared with control group. After FOLFOX application left ventricular ejection fraction significantly decreased by 9.5 % in the control group, while supplementation with melatonin and glycine alone and their combination significantly rescued heart function (p < 0.001, p = 0.013 and p = 0.023, respectively). Conclusions: In this study potential inhibitory effect of melatonin and glycine supplementation on CRLM growth was demonstrated, most likely due to inhibition of angiogenesis in cancer tissue with significant cancer cell proliferation reduction. Additionally, melatonin was found to exert immunomodulatory effects possibly influencing further tumour progression. Moreover, this study demonstrated beneficial properties of melatonin and glycine for protection against toxic effects on heart function of FOLFOX chemotherapy.

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