Antitumor potential of Alchemilla vulgaris L. in ortotopic mouse breast cancer model

Abstract

Alchemilla vulgaris L. has long history of usage in folk medicine especially against gynecological problems. Ethnomedicinal reports for the territory of Balkan are mentioning its well known biological properties against dysmenorrhea, menopausal complaints, infertility, cysts and endometriosis. Based on ethnomedicinal data on female illnesses, the objective of our study was to determine the effect of Alchemilla vulgaris L. ethanol extract against breast cancer cells in vitro and in vivo. Our results have showed remarkable viability decrease of mouse (4T1) breast cancer cells in dose‐dependent manner after the treatment with Alchemilla vulgaris L. extract. Strong inhibition of cell prolifertion was observed in treated cells. In parallel with this, different types of cell death was found. Certain percentage of 4T1 cells was subjected to programmed cell death‐apoptosis which was followed with caspase activation and confirmed by fluorescent microscopy observing tipical morphologicas features of apoptosis in treated culture. Estimation of the presence of autophagosomes shown that autophagy contributing to the cytotoxicity of the treatment. Also, enhanced production of ROS and intracellular NO after treatment with Alchemilla vulgaris L. was found. In parallel, metastatic potential of this cells is diminished. Apart from the direct effect of A. Vulgaris L. extract on tumor cells, strong potentiation of antitumor immune responce manifested dominantly through enhanced accumulation of activated dendritic cells and subsequently CD8+ T cells in spleen and tumor microenvironment. Above briefly described mode of action of Alchemilla vulgaris L. against breast cancer cells makes this plant worthwhile for further evaluation in the field of oncology.