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

Mostafa A Askar; Gharieb S El-Sayyad; Mona S Guida; Eman Khalifa; El Shaimaa Shabana; Ibrahim Y Abdelrahman

doi:10.1186/s12906-023-03986-x

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

BMC Complement Med Ther. 2023 May 20;23(1):162. doi: 10.1186/s12906-023-03986-x.

Authors

Mostafa A Askar¹, Gharieb S El-Sayyad², Mona S Guida³, Eman Khalifa⁴, El Shaimaa Shabana³, Ibrahim Y Abdelrahman⁵

Affiliations

¹ Radiation Biology Department, National Centre for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), Cairo, 11787, Egypt. mostafa_asker2@yahoo.com.
² Drug Microbiology Lab, Drug Radiation Research Department, National Center for Radiation Research and Technology, (NCRRT), Egyptian Atomic Energy Authority (EAEA), Cairo, 11787, Egypt.
³ Unit of Genetics, University Pediatrics Hospital, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt.
⁴ Oral Biology Department, Faculty of Oral & Dental Medicine, Delta University for Science and Technology, Mansoura, 11152, Egypt.
⁵ Radiation Biology Department, National Centre for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), Cairo, 11787, Egypt. ebtalah@gmail.com.

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.

Keywords: Amygdalin; Anticancer; Immunosuppressive modulators; Nanoparticles; Radio-sensitization; Tumor promoting factors.

MeSH terms

Amygdalin* / pharmacology
Amygdalin* / therapeutic use
Breast Neoplasms* / drug therapy
Breast Neoplasms* / radiotherapy
Cell Proliferation
Female
Humans
Nanoparticles*
Vascular Endothelial Growth Factor A

Substances

Amygdalin
Vascular Endothelial Growth Factor A