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Cinnamaldehyde Impacts Key Cellular Signaling Pathways for Induction of Programmed Cell Death in High-grade and Low-grade Human Glioma Cells

Overview
Journal BMC Res Notes
Publisher Biomed Central
Date 2025 Jan 20
PMID 39833890
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Abstract

Objective: Primary tumors of the brain and a large percent of malignant brain tumors are gliomas. Gliomas comprise high-grade gliomas like glioblastoma multiforme (GBMs), many of which have mutation in the tumor suppressor p53 gene and low-grade gliomas (LGGs). LGGs can progress to GBMs due to various factors. The available treatment options for GBMs and LGGs include surgical resection, radiation and chemotherapy. The chemotherapeutic drug available in the clinic is temozolomide (TMZ). However, TMZ can cause damage to DNA if taken for prolonged period. This warrants the discovery of drugs that would potentially elicit less adverse side effects while maintaining anticancer activity. To this end, we evaluated the impact of cinnamaldehyde (CA), a single, purified component of the natural product cinnamon.

Results: The elucidation of the mechanism of action revealed the impact of CA on reactive oxygen species (ROS) levels. Moreover, its effect on the extrinsic programmed cell death pathway resulted in the increase of apoptotic cell populations, invoking multicaspase. Notably, the cell survival/death pivotal molecule Bcl-2 was impacted. These effects were observed in both the types of brain tumor cells studied: GBMs, represented by U251 cells (p53 mutated cell line) and LGGs represented by H4 cells. Results from the current study suggest potential for CA as a therapeutic option as it is expected to have fewer adverse side effects due to it being a component of a natural product and possibly deter the progression of LGGs to GBMs.

References
1.
Lin L, Tai C, Chang S, Chen J, Wu S, Lin C . Cinnamaldehyde-induced apoptosis in human hepatoma PLC/PRF/5 cells involves the mitochondrial death pathway and is sensitive to inhibition by cyclosporin A and z-VAD-fmk. Anticancer Agents Med Chem. 2013; 13(10):1565-74. DOI: 10.2174/18715206113139990144. View

2.
Srivastava S, Patil K, Thompson E, Nakhai S, Kim Y, Haynes C . Disruption of Glioblastoma Multiforme Cell Circuits with Cinnamaldehyde Highlights Potential Targets with Implications for Novel Therapeutic Strategies. Cells. 2023; 12(9). PMC: 10177046. DOI: 10.3390/cells12091277. View

3.
Johnson D, Patrick ONeill B . Glioblastoma survival in the United States before and during the temozolomide era. J Neurooncol. 2011; 107(2):359-64. DOI: 10.1007/s11060-011-0749-4. View

4.
Oberheim Bush N, Chang S . Treatment Strategies for Low-Grade Glioma in Adults. J Oncol Pract. 2016; 12(12):1235-1241. DOI: 10.1200/JOP.2016.018622. View

5.
Furnari F, Fenton T, Bachoo R, Mukasa A, Stommel J, Stegh A . Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes Dev. 2007; 21(21):2683-710. DOI: 10.1101/gad.1596707. View