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Determination of Rutin's antitumoral effect on EAC solid tumor by AgNOR count and PI3K/AKT/mTOR signaling pathway

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Abstract

Rutin is one of the flavonoids found in fruits and vegetables. The PI3K/AKT/mTOR signaling pathway is critical for the life cycle at the cellular level. In current study, we purposed to demonstrate the antitumoral effect of rutin at different doses through the mTOR-signaling pathway and argyrophilic nucleolar regulatory region. EAC cells were injected subcutaneously into the experimental groups. 25 and 50 mg/kg Rutin were injected intraperitoneally to the animals with solid tumors for 14 days. Immunohistochemical, Real-time PCR and AgNOR analyzes were actualized on the taken tumors. When the rutin given groups and the tumor group were compared, the tumor size increase was detected to be statistically significant (p < 0.05). In immunohistochemical analysis, a significant decrease was encountered in the AKT, mTOR, PI3K and F8 expressions especially in the groups administered 25 mg Rutin, in comparison with the control group (p < 0.05). AgNOR area/nuclear area (TAA/NA) and average AgNOR number were determineted, and statistically important differences were detected between the groups in terms of TAA/NA ratio (p < 0.05). There were significant statistical differences between the mRNA quantity of the PI3K, AKT1 and mTOR genes (p < 0.05). In the in vitro study, cell apoptosis was evaluated with different doses of annexin V and it was determined that a dose of 10 µg/mL Rutin induced apoptosis (p < 0.05). In our study, it was demonstrated in vivo and in vitro that Rutin has an anti-tumor effect on the development of solid tumors formed by both EAC cells.

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Data Availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgments

Thanks to Yozgat Bozok University Scientific Research Projects Coordination Unit for financial support for the project.

Funding

This project was financially supported by Yozgat Bozok University Scientific Research Projects Coordination Unit (Grant Number: 6602c-TF/21-480).

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Authors and Affiliations

  1. Department of Anatomy, Faculty of Medicine, Yozgat Bozok University, 66100, Yozgat, Turkey

    Seher Yılmaz & Şükrü Ateş

  2. Department of Histology and Embriology, Faculty of Medicine, Yozgat Bozok University, 66100, Yozgat, Turkey

    Züleyha Doğanyiğit & Aslı Okan Oflamaz

  3. Department of Medical Biology, Faculty of Medicine, Afyonkarahisar Health Sciences University, 03100, Afyon, Turkey

    Evrim Suna Arıkan Söylemez

  4. Department of Anatomy, Faculty of Medicine, Erciyes University, Kayseri, Turkey

    Mehtap Nisari

  5. Institute of Biomedical and Genetic Engineering (IBGE), Islamabad, Pakistan

    Ammad Ahmad Farooqı

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  1. Seher Yılmaz
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  2. Züleyha Doğanyiğit
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Contributions

Material preparation, conceptualization and project administration were performed by [SY] and [ZD]. Data collection and analysis, validation were performed by [AOO], [ŞA] and [ESAS]. Writing—Review & Editing were performed by [MN] and [AAF]. All authors read and approved the final manuscript.

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Correspondence to Seher Yılmaz.

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The stage of the study on experimental animals was carried out in accordance with the decision numbered 20/105 taken from the Animal Experiments Local Ethics Committee of Erciyes University (Decision date: 12.08.2020).

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Yılmaz, S., Doğanyiğit, Z., Oflamaz, A.O. et al. Determination of Rutin's antitumoral effect on EAC solid tumor by AgNOR count and PI3K/AKT/mTOR signaling pathway. Med Oncol 40, 131 (2023). https://doi.org/10.1007/s12032-023-01999-7

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