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Mitigation of Breast Cancer Cells' Invasiveness Via Down Regulation of ETV7, Hippo, and PI3K/mTOR Pathways by Vitamin D3 Gold-Nanoparticles

Overview
Journal Int J Mol Sci
Publisher MDPI
Date 2024 May 25
PMID 38791386
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Abstract

Metastasis in breast cancer is the major cause of death in females (about 30%). Based on our earlier observation that Vitamin D3 downregulates mTOR, we hypothesized that Vitamin D3 conjugated to gold nanoparticles (VD3-GNPs) reduces breast cancer aggressiveness by downregulating the key cancer controller PI3K/AKT/mTOR. Western blots, migration/invasion assays, and other cell-based, biophysical, and bioinformatics studies are used to study breast cancer cell aggressiveness and nanoparticle characterization. Our VD3-GNP treatment of breast cancer cells (MCF-7 and MDA-MB-231) significantly reduces the aggressiveness (cancer cell migration and invasion rates > 45%) via the simultaneous downregulation of ETV7 and the Hippo pathway. Consistent with our hypothesis, we, indeed, found a downregulation of the PI3K/AKT/mTOR pathway. It is surprising that the extremely low dose of VD3 in the nano formulation (three orders of magnitude lower than in earlier studies) is quite effective in the alteration of cancer invasiveness and cell signaling pathways. Clearly, VD3-GNPs are a viable candidate for non-toxic, low-cost treatment for reducing breast cancer aggressiveness.

References
1.
Veeresh P, Basavaraju C, Dallavalasa S, Anantharaju P, Natraj S, Sukocheva O . Vitamin D3 Inhibits the Viability of Breast Cancer Cells In Vitro and Ehrlich Ascites Carcinomas in Mice by Promoting Apoptosis and Cell Cycle Arrest and by Impeding Tumor Angiogenesis. Cancers (Basel). 2023; 15(19). PMC: 10571758. DOI: 10.3390/cancers15194833. View

2.
Clogston J, Patri A . Zeta potential measurement. Methods Mol Biol. 2010; 697:63-70. DOI: 10.1007/978-1-60327-198-1_6. View

3.
Sengupta S, Peterson T, Sabatini D . Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress. Mol Cell. 2010; 40(2):310-22. PMC: 2993060. DOI: 10.1016/j.molcel.2010.09.026. View

4.
Gombart A, Pierre A, Maggini S . A Review of Micronutrients and the Immune System-Working in Harmony to Reduce the Risk of Infection. Nutrients. 2020; 12(1). PMC: 7019735. DOI: 10.3390/nu12010236. View

5.
Zhao C, Zeng C, Ye S, Dai X, He Q, Yang B . Yes-associated protein (YAP) and transcriptional coactivator with a PDZ-binding motif (TAZ): a nexus between hypoxia and cancer. Acta Pharm Sin B. 2020; 10(6):947-960. PMC: 7332664. DOI: 10.1016/j.apsb.2019.12.010. View