Lovastatin and perillyl alcohol inhibit glioma cell invasion, migration, and proliferation – Impact of Ras-/Rho-prenylation

Afshordel, Sarah; Kern, Beatrice; Clasohm, Jasmin; König, Hildegard; Priester, Maike; Weissenberger, Jakob; Kögel, Donat; Eckert, Gunter P.

doi:10.1016/j.phrs.2014.11.006

Cited by 58 publications

(51 citation statements)

References 51 publications

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“…This illustrates the diverse ways in which Rho GTPases can be targeted in cancer therapy. Other drugs can target the spatial regulation of Rho proteins by interfer-ing with posttranslational modifications necessary for Rho GTPase activity [120].…”

Section: Targeted Therapymentioning

confidence: 99%

The Role of Rho GTPases in Motility and Invasion of Glioblastoma Cells

Al-Koussa

Atat

Jaafar

et al. 2020

Analytical Cellular Pathology

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Astrocytomas are primary malignant brain tumors that originate from astrocytes. Grade IV astrocytoma or glioblastoma is a highly invasive tumor that occur within the brain parenchyma. The Rho family of small GTPases, which includes Rac1, Cdc42, and RhoA, is an important family whose members are key regulators of the invasion and migration of glioblastoma cells. In this review, we describe the role played by the Rho family of GTPases in the regulation of the invasion and migration of glioblastoma cells. Specifically, we focus on the role played by RhoA, Rac1, RhoG, and Cdc42 in cell migration through rearrangement of actin cytoskeleton, cell adhesion, and invasion. Finally, we highlight the importance of potentially targeting Rho GTPases in the treatment of glioblastoma.

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Section: Targeted Therapymentioning

confidence: 99%

The Role of Rho GTPases in Motility and Invasion of Glioblastoma Cells

Al-Koussa

Atat

Jaafar

et al. 2020

Analytical Cellular Pathology

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“…Recent studies have indicated that the incidence of glioma is considerably decreased in those who are administered with long-term statins. Moreover, statins can promote the apoptosis of glioma cells and suppress the proliferation of tumor cells [18,[25][26][27].…”

Section: Effect Of Statins On Glioma Cell Proliferationmentioning

confidence: 99%

“…In addition, statins have been proven to exert multiple biological functions including anti-inflammation [10], anti-oxidant [11,12], angiogenic and vascular protection [13,14], and anti-cancer effects [15][16][17][18][19]. Previous studies have indicated the potential chemo-preventive role of statins upon the risk of malignant tumors and statins can reduce the mortality rate of cancer patients and the incidence rate of gliomas [15][16][17][18][19][20][21][22]. Previous laboratory studies have demonstrated that statins can exert anti-tumor effect through inhibiting the growth, cellular proliferation and migration by inducing cellular apoptosis [15,18,[23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have indicated the potential chemo-preventive role of statins upon the risk of malignant tumors and statins can reduce the mortality rate of cancer patients and the incidence rate of gliomas [15][16][17][18][19][20][21][22]. Previous laboratory studies have demonstrated that statins can exert anti-tumor effect through inhibiting the growth, cellular proliferation and migration by inducing cellular apoptosis [15,18,[23][24][25][26]. In this article, we summarized the most recent studies related to the role of statins in gliomas, aiming to unravel the potential mechanism underlying the anti-glioma effect of statins.…”

Section: Introductionmentioning

confidence: 99%

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Application of statins in management of glioma: Recent advances

Xu¹,

Liu²,

Wang³

et al. 2018

Trop. J. Pharm Res

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Gliomas are common primary intra-cerebral tumors in adults, and seriously threaten the health and life of affected patients, especially highly-malignant gliomas, such as glioblastoma multiforme. The clinical prognosis of glioma patients is poor, even for those who have received comprehensive treatment including surgery and concurrent chemo-and/or radio-therapy. As a structural analog of β-hydroxy-βmethylglutaryl coenzyme A (HMG CoA) reductase, statins are a restrictive enzyme in the metabolism of cholesterol. Recent laboratory studies and clinical trials have demonstrated that statins can exert antitumor effect, improve clinical prognosis and significantly prolong the survival time of glioma patients. This article is aimed to highlight the mechanisms of the anti-glioma effect of statins and review recent advances in the management of the disease. This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest

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“…1 Perillyl alcohol (POH), a monoterpene isolated from the essential oils of several plants and fruits, has been recognized to impact this pathway via the inhibition of mevalonate metabolism, which synthesizes isoprenoids that are essential for posttranslational modification of the Ras proteins. 2 The anticancer potency of POH has been well established in numerous preclinical models. 3,4 Based on the prevalence of activating Ras oncogene mutations in lung cancer, prior studies also included this tumor model.…”

mentioning

confidence: 99%

Simultaneous measurement of perillyl alcohol and its metabolite perillic acid in plasma and lung after inhalational administration in Wistar rats

Lima

Rodrigues

Boaventura

et al. 2020

Drug Testing and Analysis

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The inhalational administration of drugs is a practical and non-invasive approach with the potential to reduce side effects and with a quick onset of therapeutic activity.Perillyl alcohol (POH) is a monoterpene with antitumor activity that currently is undergoing clinical evaluation as an inhalational anticancer agent. A detection method was developed that will be applicable to pharmacokinetic studies of not only POH, but also its longer-lived main metabolite, perillic acid (PA), in lung tissue and plasma after inhalational delivery. The anticancer activity of POH was investigated in vitro with the use of various lung cancer cell lines. Toxicity was established by a standard MTT assay, and apoptosis markers were analyzed by Western blot. For the detection of POH and PA in lungs and plasma, albino Wistar rats were used that were exposed to POH inhalation. Tissues were subjected to chromatographic separation on an Agilent Zorbax Eclipse XDB C 18 column, followed by detection of absorption in the ultraviolet (UV) range. In vitro, POH exerted cytotoxic activity against six different lung tumor cell lines, and apoptotic cell death was indicated by induction of active caspase 3 and cleavage of poly (ADP-ribose) polymerase 1 (PARP1). These results demonstrate that inhalational delivery of POH results in effective biodistribution and metabolism of POH in the systemic circulation. In addition, our study introduces a simple, rapid HPLC-UV method with high accuracy for simultaneous detection of POH and its metabolite PA in plasma, and for sensitive detection of PA in lung tissue, which should prove useful for applications in clinical studies. K E Y W O R D SHPLC, inhalation, perillic acid, perillyl alcohol, Ras oncoprotein

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Lovastatin and perillyl alcohol inhibit glioma cell invasion, migration, and proliferation – Impact of Ras-/Rho-prenylation

Cited by 58 publications

References 51 publications

The Role of Rho GTPases in Motility and Invasion of Glioblastoma Cells

The Role of Rho GTPases in Motility and Invasion of Glioblastoma Cells

Application of statins in management of glioma: Recent advances

Simultaneous measurement of perillyl alcohol and its metabolite perillic acid in plasma and lung after inhalational administration in Wistar rats

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