Open Access

ARTICLE

Inhibition of Ehrlich ascites carcinoma growth by melatonin: Studies with micro-CT

SEHER YILMAZ^1,2,*, ZÜLEYHA DOĞANYIĞIT³, MERT OCAK⁴, EVRIM SUNA ARIKAN SÖYLEMEZ⁵, ASLI OKAN OFLAMAZ³, SÜMEYYE UÇAR⁶, ŞÜKRÜ ATE޹, AMMAD AHMAD FAROOQI⁷

1 Department of Anatomy, Faculty of Medicine, Yozgat Bozok University, Yozgat, Turkey
2 Department of Mechanical and Aerospace Engineering, Case Western Reserve University, Cleveland, Ohio, USA
3 Department of Histology and Embriology, Faculty of Medicine, Yozgat Bozok University, Yozgat, Turkey
4 Department of Anatomy, Faculty of Dentistry, Ankara University, Ankara, Turkey
5 Department of Medical Biology, Faculty of Medicine, Afyonkarahisar Health Sciences University, Afyon, Turkey
6 Department of Anatomy, Faculty of Medicine, Erciyes University, Kayseri, Turkey
7 Department of Molecular Oncology, Institute of Biomedical and Genetic Engineering (IBGE), Islamabad, Pakistan

* Corresponding Author: SEHER YILMAZ. Email:

Oncology Research 2024, 32(1), 175-185. https://doi.org/10.32604/or.2023.042350

Received 27 May 2023; Accepted 16 August 2023; Issue published 15 November 2023

Abstract

Melatonin is a versatile indolamine synthesized and secreted by the pineal gland in response to the photoperiodic information received by the retinohypothalamic signaling pathway. Melatonin has many benefits, such as organizing circadian rhythms and acting as a powerful hormone. We aimed to show the antitumor effects of melatonin in both in vivo and in vitro models through the mammalian target of rapamycin (mTOR) signaling pathway and the Argyrophilic Nucleolar Regulatory Region (AgNOR), using the Microcomputed Tomography (Micro CT). Ehrlich ascites carcinoma (EAC) cells were administered into the mice by subcutaneous injection. Animals with solid tumors were injected intraperitoneally with 50 and 100 mg/kg melatonin for 14 days. Volumetric measurements for the taken tumors were made with micro-CT imaging, immunohistochemistry (IHC), real-time polymerase chain reaction (PCR) and AgNOR. Statistically, the tumor tissue volume in the Tumor+100 mg/kg melatonin group was significantly lower than that in the other groups in the data obtained from micro-CT images. In the IHC analysis, the groups treated with Tumor+100 mg/kg melatonin were compared when the mTOR signaling pathway and factor 8 (F8) expression were compared with the control group. It was determined that there was a significant decrease (p < 0.05). Significant differences were found in the total AgNOR area/nuclear area (TAA/NA) ratio in the treatment groups (p < 0.05). Furthermore, there were significant differences between the amount of mTOR mRNA for the phosphatidylinositol 3-kinase (PI3K), AKT Serine/Threonine Kinase (PKB/AKT) genes (p < 0.05). Cell apoptosis was evaluated with Annexin V in an in vitro study with different doses of melatonin; It was observed that 100 µg/mL melatonin dose caused an increase in the apoptotic cell death. In this study, we have reported anti-tumor effects of melatonin in cell culture studies as well as in mice models. Comprehensive characterization of the melatonin-mediated cancer inhibitory effects will be valuable in advancing our fundamental molecular understanding and translatability of pre-clinical findings to earlier phases of clinical trials.

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