Antitumoral and Immunomodulatory Effect of Mahonia aquifolium Extracts.

Andra Diana Andreicuț,Eva Fischer-Fodor,Alina Elena Pârvu,Marcel Pârvu,Adrian Bogdan Ţigu,Florinela Adriana Cătoi,Alexandru Irimie,Mihai Cenariu

doi:10.1155/2019/6439021

Abstract

The prodrug potential of Mahonia aquifolium, a plant used for centuries in traditional medicine, recently gained visibility in the literature, and the activity of several active compounds isolated from its extracts was studied on biologic systems in vitro and in vivo. Whereas the antioxidative and antitumor activities of M. aquifolium-derived compounds were studied at some extent, there are very few data about their outcome on the immune system and tumor cells. To elucidate the M. aquifolium potential immunomodulatory and antiproliferative effects, the bark, leaf, flower, green fruit, and ripe fruit extracts from the plant were tested on peripheral blood mononuclear cells and tumor cells. The extracts exert fine-tuned control on the immune response, by modulating the CD25 lymphocyte activation pathway, the interleukin-10 signaling, and the tumor necrosis-alpha secretion in four distinct human peripheral blood mononuclear cell (PBMC) subpopulations. M. aquifolium extracts exhibit a moderate cytotoxicity and changes in the signaling pathways linked to cell adhesion, proliferation, migration, and apoptosis of the tumor cells. These results open perspectives to further investigation of the M. aquifolium extract prodrug potential.

Highlights

In the tumor microenvironment (TME), tumor intrinsic factors and tumor extrinsic factors work together to induce immunosuppression
The tumor cells use autocrine or paracrine signals in order to stimulate the expression of immune checkpoints (ICs) [1, 2] on immune cells and to upregulate immunosuppressive cell recruitment and activation [3]
The phytochemical profile of plant extracts differs depending on the plant and the particular organ of a given plant [28]and of the extraction method [29]; the aim of the study was to test if M. aquifolium bark, leaf, flower, green fruit, and ripe fruit extracts can influence the TME in order to increase the antitumor responses

Summary

Introduction

In the tumor microenvironment (TME), tumor intrinsic factors and tumor extrinsic factors work together to induce immunosuppression. The composition of TME depends on the cancer types and disease stages. The tumor cells chronically secrete tumor intrinsic factors. Some of them induce reduction of the immune effector cell activity and promote immune evasion by decreasing the expression of antigenpresenting molecules and by expressing neoantigens. The tumor cells use autocrine or paracrine signals in order to stimulate the expression of immune checkpoints (ICs) [1, 2] on immune cells and to upregulate immunosuppressive cell recruitment and activation [3]. The tumor cells secrete cytokines and growth factors that promote tumor growth, angiogenesis, and metastasis [4]

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Methods

Conclusion