Zinc-Phosphate Nanoparticles as a Novel Anticancer Agent: An In Vitro Evaluation of Their Ability to Induce Apoptosis
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Zinc-Phosphate Nanoparticles as a Novel Anticancer Agent: An In Vitro Evaluation of Their Ability to Induce Apoptosis Sedigheh Vafaei 1 & Seyed Ataollah Sadat Shandiz 1 & Zeinab Piravar 1
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract In the current study, zinc-phosphate nanoparticles (ZnPNPs) were investigated for the first time due to their anticancer activity against breast cancer Michigan Cancer Foundation-7 (MCF-7) cell line. The modification of such nanoparticles (NPs) was further examined for physicochemical characterization using various techniques such as powder X-ray diffraction (XRD), dynamic light scattering (DLS), zeta potential calculation, field emission scanning electron microscopy (FESEM), energy-dispersed spectroscopy (EDS), and Fourier transform infrared (FTIR) spectroscopy. Then, the newly fabricated ZnPNPs were tested for their in vitro cell cytotoxicity against breast cancer MCF-7 cells and noncancerous human embryonic kidney HEK293 cells, using MTT assay as a colorimetric one to assess cell metabolic activity for 24 h. The apoptotic efficacy of the NPs was subsequently confirmed through data obtained from Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining kit and cell cycle analysis. Determination of reactive oxygen species (ROS) generation was further performed via flow cytometry. Additionally, the expression of tumor suppressor genes p53 was analyzed using real-time polymerase chain reaction (PCR). Also, the prepared NPs showed a mean particle size of 38 nm. The measurements correspondingly showed that the cytotoxicity of MCF-7 cells depends on the concentration of NPs (IC50 = 80.112 μg/mL). MCF-7 cells were associated with initiation of apoptotic pathway in cells. Additionally, flow cytometry revealed cell cycle arrest in sub-G1 phase. ROS production was also obtained after treatment with IC50 concentration. According to annexin V-FITC/PI staining kit data, the percentage of early and late apoptotic cells was 78.2% in those treated with ZnPNPs. Moreover, the real-time PCR results demonstrated the ability of NPs in upregulating p53 gene expression. In summary, the data demonstrated that fabricated ZnPNPs had prominence to act as antitumor agents in breast cancer therapy. Keywords Zinc-phosphate nanoparticles . Apoptosis . Cytotoxic . MCF-7 . P53
Introduction According to the GLOBOCAN 2018, as a project of the International Agency for Research on cancer (IARC), it was estimated that 18.1 million new cases and 9.6 million cancer related-deaths happened in 2018. Annual mortality rates due to cancer are also expected to rise to 17 million worldwide, and there will be 26 million new cases of cancer in 2030. Among women, breast cancer has been recognized as the most frequent cause of death, and is also the most frequently
* Seyed Ataollah Sadat Shandiz [email protected] 1
Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran
diagnosed cancer followed by colorectal and lung cancers [1, 2]. Recent
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