Amygdalin-folic acid-nanoparticles inhibit the proliferation of breast cancer and enhance the effect of radiotherapy through the modulation of tumor-promoting factors/ immunosuppressive modulators in vitro

Abstract

Introduction 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 nanomedicines 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-sensitizer efficacy of amygdalin-folic acid nanoparticles (Amy-F) on MCF-7 and MDA-MB-231 cells. Materials and methods The effects of Amy-F on MCF-7 and MDA-MB-231 cell 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 been shown to suppress the expression of the cluster of differentiation (CD4 and CD80), and interfere 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.

Amygdalin as a Promising Anticancer Agent: Molecular Mechanisms and Future Perspectives for the Development of New Nanoformulations for Its Delivery

“…Amygdalin has been shown to induce apoptosis and inhibit the adhesion of breast cancer cells by increasing the level of pro-apoptotic Bax proteins and caspase-3 activity and decreasing the level of the anti-apoptotic Bcl-2 protein [ 20 ]. Significantly, in both MCF-7 and MDA-MB-231 breast cancer cells, amygdalin significantly increased apoptosis by suppressing cell proliferation and improving radiotherapy efficiency through induction of cell cycle arrest (in G1 and sub-G1 cell cycle stages) [ 11 ]. Amygdalin was also found to decrease the migration of MDA-MB-231 cells more than MCF-7 cells [ 43 ].…”

“…At the same time, they were found to improve radiotherapy efficiency by enhancing apoptosis, blocking the cell cycle, and reducing the proliferation of breast cancer cells by downregulating iron levels and mitogen-activated protein kinases (MAPK/P38). Amygdalin–folic acid was also shown to inhibit the differentiation of CD4 and CD80 complex expression, inducing suppression of transformation of growth factor beta (TGF-beta)/interleukin-6, (IL-2)/interferon-gamma, (INF-g)/interleukin-2, and (IL-2)/vascular endothelial growth factor (VEGF) expression at the signaling pathway, while simultaneously modulating the gene expression of CD8 and the natural killer group 2D [ 11 ].…”

“…A topic of interest is the role of amygdalin, also known as vitamin B17 or laetrile (its synthetic compound), in the prevention and/or co-treatment of cancer. Several studies have demonstrated a wide range of biological properties for amygdalin, suggesting that it may exert a preventive or even a co-treatment impact on cervical, breast, prostate, lung, and bladder cancers, which may mainly be ascribed to the inhibition of cancer cell proliferation [ 9 , 10 , 11 , 12 , 13 ]. Both in vitro and in vivo evaluations of the biological actions of amygdalin extracts from three cassava ( Manihot esculenta ) cultivars grown in Benin demonstrated that this naturally occurring molecule may act effectively in cancer prevention and co-treatment by suppressing the formation of cancer cells [ 14 ].…”

Biocompatibility and radiosensitivity of a fiber optical-based dosimeter: biological applications

“…All the rats were irradiated with gamma rays by a single exposure to 2 Gy at a dose rate of 5.8 mGy /sec. using a 137 Cs source (Gamma-cell-40 Exactor; NCRRT, EAEA, Cairo, Egypt) [ 35 , 36 ].…”