Title:FA-HA-Amygdalin@Fe2O3 and/or γ-Rays Affecting SIRT1 Regulation of
YAP/TAZ-p53 Signaling and Modulates Tumorigenicity of MDA-MB231
or MCF-7 Cancer Cells
Volume: 23
Issue: 2
Author(s): Mohamed K. Abdel-Rafei*, Moustafa A. Askar, Khaled S. Azab*, Gharieb S. El-Sayyad*, Mohamed Abd El Kodous, Neama M. El Fatih, Ghada El Tawill and Noura M. Thabet
Affiliation:
- Radiation Biology Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic
Energy Authority, Cairo 11787, Egypt
- Radiation Biology Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic
Energy Authority, Cairo 11787, Egypt
- Drug Radiation Research Department, National Center for Radiation Research
and Technology (NCRRT), Egyptian Atomic Energy Authority, Cairo 11787, Egypt
Keywords:
Amygdalin, iron oxide, nano-core-shell, radiation, YAP/TAZ, SIRT1, P53.
Abstract:
Background: Breast cancer (BC) has a complex and heterogeneous etiology, and the emergence
of resistance to conventional chemo-and radiotherapy results in unsatisfactory outcomes during
BC treatment. Targeted nanomedicines have tremendous therapeutic potential in BC treatment over
their free drug counterparts.
Objective: Hence, this study aimed to evaluate the newly fabricated pH-sensitive multifunctional FAHA-
Amygdalin@Fe2O3 nano-core-shell composite (AF nanocomposite) and/or γ-radiation for effective
localized BC therapy.
Methods: The physicochemical properties of nanoparticles were examined, including stability, selectivity,
responsive release to pH, cellular uptake, and anticancer efficacy. MCF-7 and MDA-MB-231
cells were treated with AF at the determined IC50 doses and/or exposed to γ-irradiation (RT) or were
kept untreated as controls. The antitumor efficacy of AF was proposed via assessing anti-proliferative
effects, cell cycle distribution, apoptosis, and determination of the oncogenic effectors.
Results: In a bio-relevant medium, AF nanoparticles demonstrated extended-release characteristics that
were amenable to acidic pH and showed apparent selectivity towards BC cells. The bioassays revealed
that the HA and FA-functionalized AF markedly hindered cancer cell growth and enhanced radiotherapy
(RT) through inducing cell cycle arrest (pre-G1 and G2/M) and increasing apoptosis, as well as reducing
the tumorigenicity of BCs by inhibiting Silent information regulation factor 1 (SIRT1) and restoring
p53 expression, deactivating the Yes-associated protein (YAP)/ Transcriptional coactivator
with PDZ-binding motif (TAZ) signaling axis, and interfering with the tumor growth factor- β(TGF-
β)/SMAD3 and HIF-1α/VEGF signaling hub while up-regulating SMAD7 protein expression.
Conclusion: Collectively, the novel AF alone or prior RT abrogated BC tumorigenicity.
