FA-HA-Amygdalin@Fe 2 O 3 and/or γ-Rays Affecting SIRT1 Regulation of YAP/TAZ-p53 Signaling and Modulates Tumorigenicity of MDA-MB231 or MCF-7 Cancer Cells.

Autor: Abdel-Rafei MK; Radiation Biology Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority, Cairo 11787, Egypt., Askar MA; Radiation Biology Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority, Cairo 11787, Egypt., Azab KS; Radiation Biology Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority, Cairo 11787, Egypt., El-Sayyad GS; Drug Radiation Research Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority, Cairo 11787, Egypt., El Kodous MA; Department of Electrical and Electronic Information Engineering, Toyohashi University of Technology, Toyohashi 441-8580, Japan., El Fatih NM; Radiation Biology Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority, Cairo 11787, Egypt., Tawill GE; Radiation Biology Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority, Cairo 11787, Egypt., Thabet NM; Radiation Biology Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority, Cairo 11787, Egypt.
Jazyk: angličtina
Zdroj: Current cancer drug targets [Curr Cancer Drug Targets] 2023; Vol. 23 (2), pp. 118-144.
DOI: 10.2174/1568009622666220816123508
Abstrakt: 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@Fe 2 O 3 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 IC 50 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.
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Databáze: MEDLINE
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