Carnitine-induced senescence in glioblastoma cells

Yamada, Shuichi; Matsuda, Ryosuke; Nishimura, Fusanori; Nakagawa, Ichiro; Motoyama, Yasushi; Park, Young-Su; Nakamura, Mitsutoshi; Nakase, Hiroyuki; Ouji, Yukiteru; Yoshikawa, Masahide

doi:10.3892/etm.2012.556

Cited by 6 publications

(3 citation statements)

References 26 publications

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“…Yamada et al have studied the effects of carnitine on GBM cells. According to the obtained data, carnitine had an antioxidant effect in healthy cells while inducing the process of apoptosis in GBM cells [171,172].…”

Section: L-carnitinementioning

confidence: 79%

Overcoming the blood–brain barrier for the therapy of malignant brain tumor: current status and prospects of drug delivery approaches

et al. 2022

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Besides the broad development of nanotechnological approaches for cancer diagnosis and therapy, currently, there is no significant progress in the treatment of different types of brain tumors. Therapeutic molecules crossing the blood–brain barrier (BBB) and reaching an appropriate targeting ability remain the key challenges. Many invasive and non-invasive methods, and various types of nanocarriers and their hybrids have been widely explored for brain tumor treatment. However, unfortunately, no crucial clinical translations were observed to date. In particular, chemotherapy and surgery remain the main methods for the therapy of brain tumors. Exploring the mechanisms of the BBB penetration in detail and investigating advanced drug delivery platforms are the key factors that could bring us closer to understanding the development of effective therapy against brain tumors. In this review, we discuss the most relevant aspects of the BBB penetration mechanisms, observing both invasive and non-invasive methods of drug delivery. We also review the recent progress in the development of functional drug delivery platforms, from viruses to cell-based vehicles, for brain tumor therapy. The destructive potential of chemotherapeutic drugs delivered to the brain tumor is also considered. This review then summarizes the existing challenges and future prospects in the use of drug delivery platforms for the treatment of brain tumors. Graphical Abstract

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Section: L-carnitinementioning

confidence: 79%

Overcoming the blood–brain barrier for the therapy of malignant brain tumor: current status and prospects of drug delivery approaches

et al. 2022

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“…Treatment with temozolomide causes senescence in cancer cells [37], which might explain our observation of increased levels of carnitine during treatment. Carnitines have previously been reported to lead to senescence [38] wherein the downregulation of Lpropionylcarnitine was seen after finishing treatment with chemotherapy. 1,5-pentanediamine is a diamine that has previously been reported to inhibit ornithine decarboxylase, which results in the inhibition of neuroblastoma cells and glioma cells to a lesser extent [39].…”

Section: Discussionmentioning

confidence: 99%

Biogenic Amines Profile Characterization in Glioblastoma Patients Undergoing Standard of Care Treatment

Aboud,

Liu,

Dahabiyeh

et al. 2023

Preprint

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Introduction: This study aims to characterize changes in biogenic amines patterns in glioblasto-ma patients undergoing surgery and concurrent chemoradiation to illustrate how this class of metabolites changes during different stages of standard care treatment protocol. Methods: We examined 138 plasma specimens (before surgery, 2 days after surgical resection, before starting concurrent chemoradiation, immediately after chemoradiation, and after adju-vant chemotherapy treatment) from 36 patients with isocitrate dehydrogenase (IDH) wildtype glioblastoma. Untargeted GC-TOF mass spectrometry-based metabolomics of biogenic amines was used given its superiority for identifying and quantitating small metabolites; this yielded 340 structurally identified metabolites. Results: Comparing post-surgery to pre-surgery showed increased level of 12 metabolites: Gly-codeoxycholic acid (P=7.79E-05), Betonicine (P=9.23E-05), Glycocholic acid (P=3.18E-03), 3-Cysteinylaectaminophen (P=4.95E-03), S-Methyl-3-thioacetaminophen (P=5.77E-03), Tau-rocholic acid (P=9.97E-03), N-glycine (P=0.0013), p-acetamidophenyl.beta.-D-glucuronide (P=0.0048), 2-Hydroxy-5-sulfopyridine-3-carboxylic acid (P=0.0074), Acetaminophen sulfate (P=0.0095), 2-Amino-3-methoxybenzoic acid (P=0.02), and Dehydrofelodipine (P=0.024). There were 11 compounds that were downregulated, which included Mannitol (P=1.96E-19), Sorbitol (P=2.75E-019), Linoleic acid (P=1.51E-10), 1-Methylnicotinamide (P=1.78E-09), Nudifloramide (P=2.81E-08), Hexadecanedioic acid (P=5.49E-05), 3-Hydroxybutyric acid (P=0.0002), Riluzole (0.0036), Bupivacaine (P=0.0041), Lactitol (P=0.008), and 1-hydroxymidazolam.beta.-D-glucuronide (P=0.0414). After chemoradiation, significant de-crease was uncovered in Famotidine (P=0.0074), N-Isovalerylglycine (P=0.012), and 3-Methylcrotonylglycine (P=0.0131). While significant increase was detected in N-Methylisoleucine (P=0.0011), 4-Methyl-5-thiazoleethanol (P=0.042), and 6-Hydroxycaproic acid (P=0.049). Ensemble learning models, specifically random forest (RF) and AdaBoost (AB), accurately classified treatment phases with high accuracy (RF: 0.81 ± 0.04, AB: 0.78 ± 0.05). One significant insight gleamed from these models were that the metabolites Sorbitol and N-methylisoleucine were identified as important predictive features and confirmed by SHAP analysis. Conclusion: To our knowledge, this is the first study to describe plasma biogenic amines signa-tures during different treatment phases in patients with glioblastoma. A larger study is needed to confirm the results and the potential application of this algorithm for classification of treatment responses.

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“…Treatment with temozolomide causes senescence in cancer cells [ 37 ], which might explain our observation of increased levels of carnitine during treatment. Carnitines have previously been reported to lead to senescence [ 38 ] wherein the downregulation of L-propionylcarnitine was seen after finishing treatment with chemotherapy. 1,5-pentanediamine is a diamine that has previously been reported to inhibit ornithine decarboxylase, which results in the inhibition of neuroblastoma cells and glioma cells to a lesser extent [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Profile Characterization of Biogenic Amines in Glioblastoma Patients Undergoing Standard-of-Care Treatment

Aboud,

Liu,

Dahabiyeh

et al. 2023

Biomedicines

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Introduction: Biogenic amines play important roles throughout cellular metabolism. This study explores a role of biogenic amines in glioblastoma pathogenesis. Here, we characterize the plasma levels of biogenic amines in glioblastoma patients undergoing standard-of-care treatment. Methods: We examined 138 plasma samples from 36 patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma at multiple stages of treatment. Untargeted gas chromatography–time of flight mass spectrometry (GC-TOF MS) was used to measure metabolite levels. Machine learning approaches were then used to develop a predictive tool based on these datasets. Results: Surgery was associated with increased levels of 12 metabolites and decreased levels of 11 metabolites. Chemoradiation was associated with increased levels of three metabolites and decreased levels of three other metabolites. Ensemble learning models, specifically random forest (RF) and AdaBoost (AB), accurately classified treatment phases with high accuracy (RF: 0.81 ± 0.04, AB: 0.78 ± 0.05). The metabolites sorbitol and N-methylisoleucine were identified as important predictive features and confirmed via SHAP. Conclusion: To our knowledge, this is the first study to describe plasma biogenic amine signatures throughout the treatment of patients with glioblastoma. A larger study is needed to confirm these results with hopes of developing a diagnostic algorithm.

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Carnitine-induced senescence in glioblastoma cells

Cited by 6 publications

References 26 publications

Overcoming the blood–brain barrier for the therapy of malignant brain tumor: current status and prospects of drug delivery approaches

Overcoming the blood–brain barrier for the therapy of malignant brain tumor: current status and prospects of drug delivery approaches

Biogenic Amines Profile Characterization in Glioblastoma Patients Undergoing Standard of Care Treatment

Profile Characterization of Biogenic Amines in Glioblastoma Patients Undergoing Standard-of-Care Treatment

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