The Effect of Cholesterol in MCF7 Human Breast Cancer Cells

Abstract

In the last decade, cholesterol level has been implicated in several types of cancer, including breast cancer. In the current study, we aimed to investigate the condition of lipid depletion, hypocholesterolemia or hypercholesterolemia reproduced in vitro to analyze the response of different human breast cancer cells. Thus, MCF7 as the luminal A model, MB453 as the HER2 model and MB231 as the triple-negative model were used. No effect on cell growth and viability was detected in MB453 and MB231 cells. In MCF7 cells, hypocholesterolemia (1) reduced cell growth, and Ki67 expression; (2) increased ER/PgR expression; (3) stimulated the 3-Hydroxy-3-Methylglutaryl-CoA reductase and neutral sphingomyelinase and; (4) stimulated the expression of CDKN1A gene coding cyclin-dependent kinase inhibitor 1A protein, GADD45A coding growth arrest and DNA-damage-inducible alpha protein and, PTEN gene coding phosphatase and tensin homolog. All these effects were exacerbated by the lipid-depleted condition and reversed by the hypercholesterolemic condition. The relationship between cholesterol level and sphingomyelin metabolism was demonstrated. In summary, our data suggest that cholesterol levels should be controlled in luminal A breast cancer.

Vitamin C Modifies the Phenotype of Hormone Receptor Positive/HER2 Negative Breast Cancer Cells and Induces Changes in Sphingolipid Metabolism

“…Once the effects of 0.1mM and 10mM VitC on cell viability/cell cycle genes were established, MCF7 and MB231 cell phenotype was interrogated using ER, PgR, Ki67, and HER2 immunocytochemistry. ER and PgR positivity and HER2 negativity in MCF7 control cells as well as triple negativity in MB231 control cells were confirmed [19,21]. Twenty-four hours post treatment with both 0.1mM and 10mM MCF7 cells showed an overt reduction of ER expression level (Figure 3).…”

“…A general overview of MCF7 and MB-231 cell line was recently reported [19]. Here first we wanted to ascertain the possible effect of increasing doses of VitC in MCF7 and MB231 cells with MTT assay after 48 h of cell culture.…”

“…LumA is ER+ and/or PgR+ and HER2-; LumB is further classified into LumB HER2-(ER+ and/or PgR+ and HER2-) and LumB HER2+ (ER +and/or PgR+ and HER2+). Non-LumA and B are hormone negative; TNBC is ER-, PgR-, and HER2-and has the worst prognosis of all subgroups [19]. Moreover, a triple negative claudin-low (ER-, PgR-and HER2-) subtype was described.…”

“…Moreover, a triple negative claudin-low (ER-, PgR-and HER2-) subtype was described. With both genomic and transcriptomic analyses 10 breast cancer subtypes were identified based on integrated clusters (4 ER-negative, 6 triple-negative) [19]. Two-sample Mendelian randomization (MR) study aimed at analyzing the role of antioxidants including VitC in subcategories of breast cancer as ER+ breast cancer versus ER-breast cancer showed that VitC had no effect on the risk of developing the disease [20].…”

Lipid metabolic reprogramming by traditional Chinese medicine and its role in effective cancer therapy

“…Cholesterol can be synthesized in almost all tissues of the body; the liver is the main site, and synthesis of cholesterol is primarily carried out in the cytosol and endoplasmic reticulum [23]. Acetyl-CoA is the building block for cholesterol synthesis and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) is a restriction enzyme in cholesterol synthesis that is regulated by the level of cellular free cholesterol [24]. Cholesterol can be converted into bile acids, sterol hormones, or 7-dehydrogenated cholesterol in the body, among which the transformation into bile acids is the main route of cholesterol metabolism [23].…”