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

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Breast Neoplasms*/drug therapy ; Breast Neoplasms*/pathology ; Cholecalciferol*/pharmacology ; Down-Regulation*/drug effects ; Metal Nanoparticles*/chemistry ; Neoplasm Invasiveness* ; Signal Transduction*/drug effects; Female ; Humans ; Cell Line, Tumor ; Cell Movement/drug effects ; Gene Expression Regulation, Neoplastic/drug effects ; Gold/chemistry ; Hippo Signaling Pathway ; MCF-7 Cells ; Phosphatidylinositol 3-Kinases/metabolism ; Protein Serine-Threonine Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; TOR Serine-Threonine Kinases/metabolism ; Transcription Factors/metabolism

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.

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Keywords: AKT; ETV; Hippo; PI3K; VD3-GNP treatment; mTOR; pathway

1C6V77QF41 (Cholecalciferol)
7440-57-5 (Gold)
EC 2.7.1.1 (MTOR protein, human)
EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
EC 2.7.11.1 (Protein Serine-Threonine Kinases)
EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
EC 2.7.11.1 (TOR Serine-Threonine Kinases)
0 (Transcription Factors)

Date Created: 20240525 Date Completed: 20240525 Latest Revision: 20240807

20240808

PMC11120902

10.3390/ijms25105348

38791386