Betaine induces apoptosis via ROS-independent mechanisms in U87 glioblastoma cells: a potential metabolic anticancer strategy

Neslihan Meriç; Ezgi Kar; Fatih Kar

doi:10.59313/jsr-a.1728456

Betaine induces apoptosis via ROS-independent mechanisms in U87 glioblastoma cells: a potential metabolic anticancer strategy

Abstract

Betaine (trimethylglycine), a naturally occurring osmolyte and methyl donor, has attracted attention for its potential anticancer properties through its role in cellular stress responses and epigenetic regulation. Glioblastoma multiforme (GBM) represents one of the most aggressive forms of primary brain cancer characterized by rapid progression, poor prognosis, and resistance to conventional therapies. In this study, we aimed to investigate the dose- and time-dependent cytotoxic and pro-apoptotic effects of betaine on U87 glioblastoma cells, along with its influence on oxidative stress, gene expression, and protein-level markers. U87 cells were treated with increasing concentrations of betaine, and cell viability was assessed using the MTS assay. Apoptosis was evaluated via Annexin V/PI flow cytometry, while ROS levels were measured with DCFDA staining. Quantitative RT-PCR and ELISA tests were conducted to assess gene and protein expression patterns associated with apoptosis, oxidative stress, and inflammatory signaling. Our findings demonstrated that betaine reduced U87 cell viability in a concentration-dependent fashion, triggered late apoptosis and necrotic cell death, and markedly lowered intracellular reactive oxygen species (ROS) levels. Furthermore, betaine modulated the expression of key signaling molecules including PTEN, BCL-2, AKT1, and NF-κB, while increasing mitochondrial apoptotic markers such as CASP3 and cytochrome C. Interestingly, the anticancer effects of betaine appeared to occur through ROS-independent mechanisms. The results indicate that betaine may serve as a promising anticancer agent for glioblastoma, warranting further investigation in preclinical models.

Keywords

References

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Details

Primary Language

English

Subjects

Cell Metabolism

Journal Section

Research Article

Authors

Neslihan Meriç ^*
0000-0002-2878-5052
Türkiye

Ezgi Kar
0000-0003-2134-4067
Türkiye

Fatih Kar
0000-0001-8356-9806
Türkiye

Publication Date

September 30, 2025

Submission Date

June 27, 2025

Acceptance Date

August 19, 2025

Published in Issue

Year 2025 Number: 062

DOI

https://doi.org/10.59313/jsr-a.1728456

IZ

https://izlik.org/JA22KC45NH

Cite

RIS / Bibtex

APA

Meriç, N., Kar, E., & Kar, F. (2025). Betaine induces apoptosis via ROS-independent mechanisms in U87 glioblastoma cells: a potential metabolic anticancer strategy. Journal of Scientific Reports-A, 062, 111-124. https://doi.org/10.59313/jsr-a.1728456

AMA

1.Meriç N, Kar E, Kar F. Betaine induces apoptosis via ROS-independent mechanisms in U87 glioblastoma cells: a potential metabolic anticancer strategy. JSR-A. 2025;(062):111-124. doi:10.59313/jsr-a.1728456

Chicago

Meriç, Neslihan, Ezgi Kar, and Fatih Kar. 2025. “Betaine Induces Apoptosis via ROS-Independent Mechanisms in U87 Glioblastoma Cells: A Potential Metabolic Anticancer Strategy”. Journal of Scientific Reports-A, nos. 062: 111-24. https://doi.org/10.59313/jsr-a.1728456.

EndNote

Meriç N, Kar E, Kar F (September 1, 2025) Betaine induces apoptosis via ROS-independent mechanisms in U87 glioblastoma cells: a potential metabolic anticancer strategy. Journal of Scientific Reports-A 062 111–124.

IEEE

[1]N. Meriç, E. Kar, and F. Kar, “Betaine induces apoptosis via ROS-independent mechanisms in U87 glioblastoma cells: a potential metabolic anticancer strategy”, JSR-A, no. 062, pp. 111–124, Sept. 2025, doi: 10.59313/jsr-a.1728456.

ISNAD

Meriç, Neslihan - Kar, Ezgi - Kar, Fatih. “Betaine Induces Apoptosis via ROS-Independent Mechanisms in U87 Glioblastoma Cells: A Potential Metabolic Anticancer Strategy”. Journal of Scientific Reports-A. 062 (September 1, 2025): 111-124. https://doi.org/10.59313/jsr-a.1728456.

JAMA

1.Meriç N, Kar E, Kar F. Betaine induces apoptosis via ROS-independent mechanisms in U87 glioblastoma cells: a potential metabolic anticancer strategy. JSR-A. 2025;:111–124.

MLA

Meriç, Neslihan, et al. “Betaine Induces Apoptosis via ROS-Independent Mechanisms in U87 Glioblastoma Cells: A Potential Metabolic Anticancer Strategy”. Journal of Scientific Reports-A, no. 062, Sept. 2025, pp. 111-24, doi:10.59313/jsr-a.1728456.

Vancouver

1.Neslihan Meriç, Ezgi Kar, Fatih Kar. Betaine induces apoptosis via ROS-independent mechanisms in U87 glioblastoma cells: a potential metabolic anticancer strategy. JSR-A. 2025 Sep. 1;(062):111-24. doi:10.59313/jsr-a.1728456