Antimelanoma Effects of <i>Alchemilla vulgaris</i>: A Comprehensive In Vitro and In Vivo Study
Sanja Jelača,
Ivan Jovanovic,
Dijana Bovan,
Sladjana Pavlovic,
Nevena Gajovic,
Duško Dunđerović,
Zora Dajić-Stevanović,
Aleksandar Acović,
Sanja Mijatović,
Danijela Maksimović-Ivanić
Affiliations
Sanja Jelača
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
Ivan Jovanovic
Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovića 69, 34000 Kragujevac, Serbia
Dijana Bovan
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
Sladjana Pavlovic
Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovića 69, 34000 Kragujevac, Serbia
Nevena Gajovic
Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovića 69, 34000 Kragujevac, Serbia
Duško Dunđerović
Institute of Pathology, School of Medicine, University of Belgrade, Dr Subotića 8, 11000 Belgrade, Serbia
Zora Dajić-Stevanović
Faculty of Agriculture, University of Belgrade, Nemanjina 6, 11080 Belgrade, Serbia
Aleksandar Acović
Department of Dentistry, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovića 69, 34000 Kragujevac, Serbia
Sanja Mijatović
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
Danijela Maksimović-Ivanić
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
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.
