Amygdalin folic acid nanoparticles inhibits the proliferation of breast cancer and enhances the effect of radiotherapy through modulation of tumor promoting factors/immunosuppressive modulators in vitro
Purpose: Breast Cancer (BC) cells often develop multiple mechanisms of chemo and radio-resistance during tumor progression, which is the major reason for the failure of breast cancer therapy. Targeted nano-medicines have tremendous therapeutic potential in BC treatment over their free drug counterparts. Searching for chemo-and radio sensitizers to overcome such resistance is therefore urgently required. The goal of this study is to evaluate and compare the radio-sensitizers efficacy of Amygdalin-Folic acid-nanoparticles (Amy-F) on MCF-7 and MDA-MB-231 cells.
Methods: The effects of Amy-F on MCF-7 and MDA-MB-231 cells proliferation and IC50 were assessed using MTT assay. The expression of proteins involved in several mechanisms induced by Amy-F in MCF-7 and MDA-MB-231 cells, including growth inhibition, apoptosis, tumor growth regulators, immuno-modulators and radio sensitizing activities were evaluated via flow cytometry and ELISA assay.
Results: Nanoparticles demonstrated sustained Amy-F release properties and apparent selectivity towards BC cells. Cell-based assays revealed that Amy-F markedly suppresses cancer cell growth and improves Radiotherapy (RT) through inducing cell cycle arrest (G1 and sub G1), and increases apoptosis as well as reduces the proliferation of BC by down-regulating Mitogen-Activated Protein Kinases (MAPK/P38), Iron level (Fe), Nitric Oxide (NO), and up-regulating the Reactive Oxygen Species level (ROS). Amy-F has also shown to suppress the expression of the Cluster of Differentiations (CD4 and CD80), and interfering with the Transforming growth factor beta (TGF- β)/Interferon Gamma (INF-g)/ Interleukin-2 (IL-2)/Interleukin-6 (IL-6)/Vascular Endothelial Growth Factor (VEGF) induced suppression in its signaling hub, while up-regulating Natural Killer Group 2D receptor (NKG2D) and CD8 expression.
Conclusions: Collectively, the novel Amy-F either alone or in combination with RT abrogated BC proliferation
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Prof. Elhadi Miskeen
Obstetrics and Gynaecology Faculty of Medicine, University of Bisha, Saudi Arabia
Ahmed Hussien Alshewered
University of Basrah College of Medicine, Iraq
Department of Electronics and Communication Engineering SRM University – AP, Andhra Pradesh
Supervisor of Biochemistry Lab and PhD. students of Faculty of Science, Department of Chemistry and Department of Chemis
Fava Maria Giovanna
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