Folate-targeted PTEN/AKT/P53 signaling pathway promotes apoptosis in breast cancer cells

Abstract

Objective Folate deficiency is closely related to the occurrence of human tumors and plays an important role in cell growth, differentiation, repair, and host defense. We studied the effects of folic acid on the apoptosis of breast cancer cells (MDA-MB-231) and on the activity of the PTEN/AKT/P53 signaling pathway in breast cancer cells.Methods Breast cancer cells (MDA-MB-231) were treated with folate alone or in combination with a PTEN specific inhibitor, SF1670. Cell viability was detected by a MTT assay, and the expression levels of apoptosis-related proteins and PTEN/AKT/P53 signaling pathway were detected via Western blot analysis. Rate of apoptosis was measured via cytometry.Results Folic acid inhibited the cell viability of MDAMB-231 cells and the expressions of Bcl-2 and p-AKT proteins and upregulate the expression of Bax, PTEN, and P53 proteins, thereby inducing apoptosis in these cells. SF1670 treatment inhibited the expressions of Bcl-2 and p-AKT protein and upregulate Bax, PTEN, and P53 protein expression.Conclusion Folic acid has cytotoxic effects on MDAMB-231 cells and can induce apoptosis by targeting the PTEN/AKT/P53 signaling pathway.

Methyl-Donors Can Induce Apoptosis and Attenuate Both the Akt and the Erk1/2 Mediated Proliferation Pathways in Breast and Lung Cancer Cell Lines

“…Additionally, a majority of clinical and randomized clinical trials have shown that methyl-donor micronutrient intake affects DNA methylation by reducing the risk of several cancer types [ 3 ]. Furthermore, folate can induce apoptosis via the PTEN/AKT/P53 signaling pathway, and through reducing the effects of both the AKT and ERK signaling in breast cancer [ 18 , 19 ]. It is known that AKT signaling can inhibit the activation of the pro-apoptotic Caspase-9 and Caspase-3 [ 20 ], and that upstream inhibitors of the MAPK pathway can reduce tumor proliferation and mediate apoptosis, though Erk1/2 activation may also be involved in apoptosis induction [ 21 ].…”

Composition, preparation methods, and applications of nanoniosomes as codelivery systems: a review of emerging therapies with emphasis on cancer

“…102 The developed platform is composed of dual-loaded niosomes with letrozole (Let) and cyclophosphamide (Cyclo) (NLC), and folic acid (FA) functionalized on the surface (NLCPFA) and can activate apoptosis, reduce Bcl-2 expression, and increase Bax expression by targeting the PTEN/AKT/P53 signaling pathway. 107 Niosome NPs contain an equal amount of both drugs, and formulation optimization features have been investigated using various surfactant-cholesterol molar proportions of 1 : 1 and 2 : 1 and lipid-drug molar proportions of 10 : 1 and 20 : 1, that affected the EE. 108 EE values of samples improved by 2–3% for each drug at the greater surfactant:cholesterol and lipid:drug molar proportions.…”