Effects of Lovastatin on Brain Cancer Cells

Amadasu, Efosa; Kang, Richard; Usmani, Ahsan; Borlongan, Cesario V.

doi:10.1177/09636897221102903

Cited by 9 publications

(4 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, statins deplete isoprenoids, which are required for the prenylation of small Rho GTPases in cancer cells [ 26 ]. For instance, lovastatin was reported to inhibit brain tumor stem cells, which may suppress brain tumors [ 27 ]. By interfering with the mevalonate pathway, statins were supposed to reduce the proliferation and differentiation of cancer stem cells and accelerate apoptosis [ 28 , 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

Association between the Use of Statins and Brain Tumors

Jang

Choi²,

Kwon

et al. 2023

Biomedicines

View full text Add to dashboard Cite

This study aimed to investigate the effects of statin use on the incidence of brain tumors. The Korean National Health Insurance Service—National Sample Cohort from 2005 to 2019 was used. The 1893 patients who were diagnosed with brain tumors were matched with 7572 control patients for demographic variables. The history of dyslipidemia was collected, and their history of prescription of statins before diagnosis of brain tumor was examined. The participants without dyslipidemia were set as a reference population. Then, the odds for brain tumors were analyzed in dyslipidemia patients without statin use, dyslipidemia patients who were prescribed statins for less than 365 days, and dyslipidemia patients who were prescribed statins for 365 days or more. Propensity score overlap weighted multivariable logistic regression analysis was used and adjusted for demographics and comorbidities. Secondary analyses were conducted according to types of statins, malignancy of brain tumors, and histories of demographics or comorbidities. A total of 11.78% of brain tumor patients and 10.95% of control participants had histories of statin use for 365 days or more. Dyslipidemia patients with 365 days or more duration of statin use demonstrated 1.22 times higher odds for brain tumors than normal participants (95% confidence intervals [CI] = 1.06–1.14, p = 0.007). Dyslipidemia patients with less than 365 days of statin use had higher odds of brain tumors than other groups (odds ratio = 1.60, 95% CI = 1.36–1.87, p < 0.001). The higher odds for brain tumors in short-term statin users (<365 days) than in long-term statin users (≥365 days) were consistent in secondary analyses according to types of statins, malignancy of brain tumors, and histories of demographics or comorbidities. Long-term statin use in dyslipidemia patients was related to a lower risk of brain tumors than short-term statin use in patients with dyslipidemia.

show abstract

Section: Discussionmentioning

confidence: 99%

Association between the Use of Statins and Brain Tumors

Jang

Choi²,

Kwon

et al. 2023

Biomedicines

View full text Add to dashboard Cite

show abstract

“…Of noteworthy is the report that patient-derived brain tumor initiating cells (BTIC) from glioblastoma are maintained by a Myc-regulated mevalonate pathway [26]. Similarly, the lipid-lowering drug Lovastatin is reported to possibly have an effect on glioblastoma stem cells by interfering with the mevalonate pathway [27]. Therefore, we envision that a reduction in phosphomevalonate kinase in the present study with CA could have an inhibitory effect on the maintenance of BTIC in glioblastomas, thus possibly preventing recurrence of this devastating cancer and providing a beneficial therapeutic effect.…”

Section: Discussionmentioning

confidence: 99%

Disruption of Glioblastoma Multiforme Cell Circuits with Cinnamaldehyde Highlights Potential Targets with Implications for Novel Therapeutic Strategies

Srivastava

Patil

Thompson

et al. 2023

Cells

View full text Add to dashboard Cite

Glioblastoma multiforme (GBM) is a major aggressive primary brain tumor with dismal survival outcome and few therapeutic options. Although Temozolomide (TMZ) is a part of the standard therapy, over time, it can cause DNA damage leading to deleterious effects, necessitating the discovery of drugs with minimal side effects. To this end, we investigated the effect of cinnamaldehyde (CA), a highly purified, single ingredient from cinnamon, on the GBM cell lines U87 and U251 and the neuroglioma cell line H4. On observing similar impact on the viability in all the three cell lines, detailed studies were conducted with CA and its isomer/analog, trans-CA (TCA), and methoxy-CA (MCA) on U87 cells. The compounds exhibited equal potency when assessed at the cellular level in inhibiting U87 cells as well as at the molecular level, resulting in an increase in reactive oxygen species (ROS) and an increase in the apoptotic and multicaspase cell populations. To further characterize the key entities, protein profiling was performed with CA. The studies revealed differential regulation of entities that could be key to glioblastoma cell circuits such as downregulation of pyruvate kinase-PKM2, the key enzyme of the glycolytic pathway that is central to the Warburg effect. This allows for monitoring the levels of PKM2 after therapy using recently developed noninvasive technology employing PET [18F] DASA-23. Additionally, the observation of downregulation of phosphomevalonate kinase is significant as the brain tumor initiating cells (BTIC) are maintained by the metabolism occurring via the mevalonate pathway. Results from the current study, if translated in vivo, could provide additional efficacious treatment options for glioblastoma with minimal side effects.

show abstract

“…Although a direct link between MeCP2 and brain metabolism remains to be fully explored, emerging studies that focus on DNA methylation/MeCP2 and metabolism in the context of neuronal pathologies provide insight about this relationship. Accordingly, commonly used drugs that are administered in patients to control glucose and cholesterol metabolism are subjects of study for MeCP2-associated disorders such as Rett Syndrome and other diseases of the brain such as brain tumors [ 18 , 20 , 104 , 232 , 233 , 234 , 235 ].…”

Section: The Interplay Between Mecp2 and Brain Metabolismmentioning

confidence: 99%

MeCP2 Is an Epigenetic Factor That Links DNA Methylation with Brain Metabolism

Vuu

Roberts

Rastegar

2023

IJMS

View full text Add to dashboard Cite

DNA methylation, one of the most well-studied epigenetic modifications, is involved in a wide spectrum of biological processes. Epigenetic mechanisms control cellular morphology and function. Such regulatory mechanisms involve histone modifications, chromatin remodeling, DNA methylation, non-coding regulatory RNA molecules, and RNA modifications. One of the most well-studied epigenetic modifications is DNA methylation that plays key roles in development, health, and disease. Our brain is probably the most complex part of our body, with a high level of DNA methylation. A key protein that binds to different types of methylated DNA in the brain is the methyl-CpG binding protein 2 (MeCP2). MeCP2 acts in a dose-dependent manner and its abnormally high or low expression level, deregulation, and/or genetic mutations lead to neurodevelopmental disorders and aberrant brain function. Recently, some of MeCP2-associated neurodevelopmental disorders have emerged as neurometabolic disorders, suggesting a role for MeCP2 in brain metabolism. Of note, MECP2 loss-of-function mutation in Rett Syndrome is reported to cause impairment of glucose and cholesterol metabolism in human patients and/or mouse models of disease. The purpose of this review is to outline the metabolic abnormalities in MeCP2-associated neurodevelopmental disorders that currently have no available cure. We aim to provide an updated overview into the role of metabolic defects associated with MeCP2-mediated cellular function for consideration of future therapeutic strategies.

show abstract

Effects of Lovastatin on Brain Cancer Cells

Cited by 9 publications

References 58 publications

Association between the Use of Statins and Brain Tumors

Association between the Use of Statins and Brain Tumors

Disruption of Glioblastoma Multiforme Cell Circuits with Cinnamaldehyde Highlights Potential Targets with Implications for Novel Therapeutic Strategies

MeCP2 Is an Epigenetic Factor That Links DNA Methylation with Brain Metabolism

Contact Info

Product

Resources

About