Mitochondrial-associated impairments of temozolomide on neural stem/progenitor cells and hippocampal neurons

Lomeli, Naomi; Di, Kaijun; Pearre, Diana C.; Chung, Tzu-Feng; Bota, Daniela

doi:10.1016/j.mito.2020.02.001

Cited by 22 publications

(15 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Neuronal and Glial Oxidative Stress Induced By Chemotherapeutic Drugs In Preclinical Studiesmentioning

confidence: 99%

“…Compared to in vivo studies, relatively few in vitro studies have investigated the direct effects of anticancer drugs on neurons [38][39][40]. In primary cultures of rat neural stem cells or progenitor cells and hippocampal neurons, cisplatin and temozolomide induced mitochondrial DNA damage, impaired respiratory activity, and increased oxidative stress [39,40]. However, the presence of antioxidants in the culture medium used in cell culture experiments may be sufficient to block the effect of anticancer drugs and therefore, these systems are not suitable for examining ROS-mediated neurotoxicity because they may not reflect the actual conditions of chemotherapy-treated animal models or patients.…”

Section: Neuronal and Glial Oxidative Stress Induced By Chemotherapeutic Drugs In Preclinical Studiesmentioning

confidence: 99%

“…Co-administration of different antioxidant compounds in animal models reduced oxidative stress levels and improved the cognitive deficits elicited by the administration of chemotherapeutic drugs [52][53][54]56,57,88,89]. N-acetylcysteine treatment (250 mg/kg/day) prevented free radical production, ameliorated apoptotic cellular death and dendritic spine loss, and partially reversed cisplatininduced cognitive impairments [39]. A regimen of repeated cisplatin treatment in rats led to impaired cognitive performance (contextual fear conditioning, context object discrimination, and novel object recognition tasks), but this effect was partially mitigated by concomitant N-acetylcysteine treatment [88].…”

Section: Treatment To Prevent Oxidative Stress and Cognitive Dysfunction Induced In Vivo By Chemotherapeutic Drugsmentioning

confidence: 99%

See 2 more Smart Citations

Oxidative Stress and Cognitive Alterations Induced by Cancer Chemotherapy Drugs: A Scoping Review

Cauli

2021

Antioxidants

View full text Add to dashboard Cite

Cognitive impairment is one of the most deleterious effects of chemotherapy treatment in cancer patients, and this problem sometimes remains even after chemotherapy ends. Common classes of chemotherapy-based regimens such as anthracyclines, taxanes, and platinum derivatives can induce both oxidative stress in the blood and in the brain, and these effects can be reproduced in neuronal and glia cell cultures. In rodent models, both the acute and repeated administration of doxorubicin or adriamycin (anthracyclines) or cisplatin impairs cognitive functions, as shown by their diminished performance in different learning and memory behavioural tasks. Administration of compounds with strong antioxidant effects such as N-acetylcysteine, gamma-glutamyl cysteine ethyl ester, polydatin, caffeic acid phenethyl ester, and 2-mercaptoethane sulfonate sodium (MESNA) counteract both oxidative stress and cognitive alterations induced by chemotherapeutic drugs. These antioxidant molecules provide the scientific basis to design clinical trials in patients with the aim of reducing the oxidative stress and cognitive alterations, among other probable central nervous system changes, elicited by chemotherapy in cancer patients. In particular, N-acetylcysteine and MESNA are currently used in clinical settings and are therefore attracting scientific attention.

show abstract

Section: Neuronal and Glial Oxidative Stress Induced By Chemotherapeutic Drugs In Preclinical Studiesmentioning

confidence: 99%

Section: Neuronal and Glial Oxidative Stress Induced By Chemotherapeutic Drugs In Preclinical Studiesmentioning

confidence: 99%

Section: Treatment To Prevent Oxidative Stress and Cognitive Dysfunction Induced In Vivo By Chemotherapeutic Drugsmentioning

confidence: 99%

See 1 more Smart Citation

Oxidative Stress and Cognitive Alterations Induced by Cancer Chemotherapy Drugs: A Scoping Review

Cauli

2021

Antioxidants

View full text Add to dashboard Cite

show abstract

“…Patient 6 had also been exposed to bevacizumab and temozolomide, which have been reported to impair mitochondrial function in vitro. 15,16 Asymptomatic granulomas in muscle are found in 50% to 80% of sarcoidosis patients, 17 and other etiologies should therefore be explored before making the diagnosis of sarcoid myopathy, particularly in the setting of a markedly elevated CK. The distinction between sarcoid myopathy and IMNM is crucial, as IMNM requires more aggressive therapy.…”

Section: Autophagy Pathways Have Recently Been Implicated In Imnm Asmentioning

confidence: 99%

Immune‐mediated necrotizing myopathy: Unusual presentations of a treatable disease

et al. 2021

View full text Add to dashboard Cite

Introduction/Aims: Immune-mediated necrotizing myopathy (IMNM) is an immunemediated myopathy typically presenting with progressive subacute weakness and characteristic, but nonspecific, myopathological findings. Atypical cases however can mimic other inherited or acquired myopathies, depriving patients of treatment. We describe a cohort of such patients.Methods: We retrospectively identified IMNM patients who either previously carried a diagnosis of an inherited myopathy established on clinicopathological grounds or whose muscle biopsies displayed atypical features suggestive of a different myopathy.Results: Among 131 IMNM patients, seven previously unreported patients (5%) met one of the above criteria. Three patients were diagnosed with limb-girdle muscular dystrophy on the basis of a chronic progressive course of weakness and family history of myopathy or cardiomyopathy. The other four patients displayed atypical histological features (two prominent mitochondrial abnormalities, one myofibrillar pathology, and one granulomatous inflammation). Immunostaining of biopsies from 12 additional IMNM patients did not identify myofibrillar pathology. The patient with granulomatous inflammation was known to have pulmonary sarcoidosis. Genetic testing for inherited myopathies was unrevealing. Antibodies against 3-hydroxy-3-methylglutaryl-CoA reductase or signal recognition particle were identified in 5 and 1 patients, respectively. Four patients presented with slowly progressive weakness over 3-13 y, while weakness was subacute over ≤6 mo in three patients. All patients responded to immunomodulatory therapy. Discussion: Atypical clinical and histological features can occur in IMNM patients, causing delays in diagnosis and treatment. Clinicians should, therefore, consider IMNM in the differential diagnosis of unexplained proximal myopathies in spite of atypical clinical and myopathological findings.

show abstract

“…Temozolomide is an alkylating agent used clinically for cancer therapy. It is known to induce lethal DNA damage followed by the caspase-dependent apoptosis, leading to mitochondrial depolarisation [30,31]. There was a considerable decrease of ∆ Pharmaceuticals 2021, 14, x FOR PEER REVIEW enhancer of activated B cells (NF-𝛋B) is a well helenalin, even though there are a number of p Helenalin has previously been reported to m and prevent the release of NF-𝛋B dimers, whi to numerous 𝛋B sites (the consensus sequenc rimidine, N: any base) and activate genes rela tasis and angiogenesis [7,13,14].…”

Section: Mitochondrial Responsementioning

confidence: 99%

Mechanism of Action of the Sesquiterpene Compound Helenalin in Rhabdomyosarcoma Cells

Mun

Townley

2021

Pharmaceuticals

View full text Add to dashboard Cite

Rhabdomyosarcoma (RMS) is the most frequent soft tissue sarcoma in paediatric patients. Relapsed or refractory RMS shows very low 5-year survival rates, which urgently necessitates new chemotherapy agents. Herein, the sesquiterpene lactone, helenalin, was investigated as a new potential therapeutic agent against the embryonal RMS (eRMS) and alveolar RMS (aRMS) cells. We have evaluated in vitro antiproliferative efficacy of helenalin on RMS cells by the MTT and wound healing assay, and estimated several cell death pathways by flow cytometry, confocal microscopy and immunoblotting. It was shown that helenalin was able to increase reactive oxygen species levels, decrease mitochondrial membrane potential, trigger endoplasmic reticulum stress and deactivate the NF-κB pathway. Confirmation was obtained through the use of antagonistic compounds which alleviated the effects of helenalin in the corresponding pathways. Our findings demonstrate that oxidative stress is the pivotal mechanism of action of helenalin in promoting RMS cell death in vitro.

show abstract

Mitochondrial-associated impairments of temozolomide on neural stem/progenitor cells and hippocampal neurons

Cited by 22 publications

References 61 publications

Oxidative Stress and Cognitive Alterations Induced by Cancer Chemotherapy Drugs: A Scoping Review

Oxidative Stress and Cognitive Alterations Induced by Cancer Chemotherapy Drugs: A Scoping Review

Immune‐mediated necrotizing myopathy: Unusual presentations of a treatable disease

Mechanism of Action of the Sesquiterpene Compound Helenalin in Rhabdomyosarcoma Cells

Contact Info

Product

Resources

About