Antimelanoma Effects of Alchemilla vulgaris: A Comprehensive In Vitro and In Vivo Study

Author:

Jelača Sanja1ORCID,Jovanovic Ivan2ORCID,Bovan Dijana1,Pavlovic Sladjana2,Gajovic Nevena2ORCID,Dunđerović Duško3,Dajić-Stevanović Zora4,Acović Aleksandar5ORCID,Mijatović Sanja1,Maksimović-Ivanić Danijela1ORCID

Affiliation:

1. Department of Immunology, Institute for Biological Research “Siniša Stanković”—National Institute of the Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11108 Belgrade, Serbia

2. Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovića 69, 34000 Kragujevac, Serbia

3. Institute of Pathology, School of Medicine, University of Belgrade, Dr Subotića 8, 11000 Belgrade, Serbia

4. Faculty of Agriculture, University of Belgrade, Nemanjina 6, 11080 Belgrade, Serbia

5. Department of Dentistry, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovića 69, 34000 Kragujevac, Serbia

Abstract

Due to the rich ethnobotanical and growing evidence-based medicine records, the Alchemillae herba, i.e., the upper parts of the Lady’s mantle (Alchemilla vulgaris L.), was used for the assessment of antimelanoma activity. The ethanolic extract of A. vulgaris strongly suppressed the viability of B16F1, B16F10, 518A2, and Fem-X cell lines. In contrast to the in vitro study, where the B16F1 cells were more sensitive to the treatment than the more aggressive counterpart B16F10, the results obtained in vivo using the corresponding syngeneic murine model were quite the opposite. The higher sensitivity of B16F10 tumors in vivo may be attributed to a more complex response to the extract compared to one triggered in vitro. In addition, the strong immunosuppressive microenvironment in the B16F1 model is impaired by the treatment, as evidenced by enhanced antigen-presenting potential of dendritic cells, influx and activity of CD4+ T and CD8+ T lymphocytes, decreased presence of T regulatory lymphocytes, and attenuation of anti-inflammatory cytokine production. All these effects are supported by the absence of systemic toxicity. A. vulgaris extract treatment results in a sustained and enhanced ability to reduce melanoma growth, followed by the restoration of innate and adopted antitumor immunity without affecting the overall physiology of the host.

Funder

Ministry of Science, Technological Development and Innovation of the Republic of Serbia

joint funding of Development and research projects of the Republic of Serbia and the People’s Republic of China

Publisher

MDPI AG

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