Valproic acid (VPA), a histone deacetylase inhibitor (HDACi), has been shown to be an effective tool in cancer treatment. Although its ability to induce apoptosis has been described in many cancer types, the data come from experiments performed in normoxic (21% O2) conditions only. Therefore, we questioned whether VPA would be equally effective under hypoxic conditions (1% O2), which is known to induce resistance to apoptosis. Four neuroblastoma cell lines were used: UKF-NB-3, SK-N-AS, plus one cisplatin-resistant subline derived from each of the two original sensitive lines. All were treated with VPA and incubated under hypoxic conditions. Measurement of apoptosis and viability using TUNEL assay and Annexin V/propidium iodide labeling revealed that VPA was even more effective under hypoxic conditions. We show here that hypoxia-induced resistance to chemotherapeutic agents such as cisplatin could be overcome using VPA. We also demonstrated that apoptosis pathways induced by VPA do not differ between normoxic and hypoxic conditions. VPA-induced apoptosis proceeds through the mitochondrial pathway, not the extrinsic pathway (under both normoxia and hypoxia), since inhibition of caspase-8 failed to decrease apoptosis or influence bid cleavage. Our data demonstrated that VPA is more efficient in triggering apoptosis under hypoxic conditions and overcomes hypoxia-induced resistance to cisplatin. The results provide additional evidence for the use of VPA in neuroblastoma (NBL) treatment.
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http://dx.doi.org/10.3892/or.2011.1577 | DOI Listing |
Zhonghua Nei Ke Za Zhi
February 2025
Department of General Medicine the First Affiliated Hospital of Soochow University, Suzhou215006,China.
To analyze the occurrence of metabolic dysfunction-associated fatty liver disease (MAFLD) and related inflammatory indicators in obstructive sleep apnea hypopnea syndrome (OSAHS) and explore the risk factors of MAFLD. A cross-sectional study. From January 2022 to October 2024,172 patients with sleep disorders were enrolled in the First Affiliated Hospital of Soochow University,including 38 patients with non-OSAHS,53 patients with mild OSAHS,37 patients with moderate OSAHS,and 44 patients with severe OSAHS.
View Article and Find Full Text PDFFree Radic Biol Med
January 2025
University of Colorado, Anschutz Medical Campus School of Medicine| Translational research laboratory of Red Blood Cell Diseases and Hypoxia related illnesses| Cardiovascular Pulmonary Research (CVP) group, Pediatrics. Electronic address:
Lung tissue from human patients and murine models of sickle cell disease pulmonary hypertension (SCD-PH) show perivascular regions with excessive iron accumulation. The iron accumulation arises from chronic hemolysis and extravasation of hemoglobin (Hb) into the lung adventitial spaces, where it is linked to nitric oxide depletion, oxidative stress, inflammation, and tissue hypoxia, which collectively drive SCD-PH. Here, we tested the hypothesis that intrapulmonary delivery of hemopexin (Hpx) to the deep lung is effective at scavenging heme-iron and attenuating the progression of SCD-PH.
View Article and Find Full Text PDFCancer Lett
January 2025
Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, 200025, China. Electronic address:
Neutrophils are pivotal in the immune system and have been recognized as significant contributors to cancer development and progression. These cells undergo metabolic reprogramming in response to various stimulus, including infections, diseases, and the tumor microenvironment (TME). Under normal conditions, neutrophils primarily rely on aerobic glucose metabolism for energy production.
View Article and Find Full Text PDFPlacenta
January 2025
Magee-Women's Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, 15213, USA; Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA, 15213, USA. Electronic address:
Introduction: Fusion of mononucleated cytotrophoblasts into syncytium leads to trophoblast senescence. Yet, premature senescence is associated with preeclampsia, fetal growth restriction (FGR), and related obstetrical syndromes. A set of 28 transcripts that comprise senescence-associated secretory phenotype (SASP) was recently described in placentas from women with preeclampsia.
View Article and Find Full Text PDFFront Biosci (Landmark Ed)
January 2025
Department of Pathology, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41500 Larissa, Greece.
Background: Hypoxia-inducible factor 1 alpha (HIF-1α) and its related vascular endothelial growth factor (VEGF) may play a significant role in atherosclerosis and their targeting is a strategic approach that may affect multiple pathways influencing disease progression. This study aimed to perform a systematic review to reveal current evidence on the role of HIF-1α and VEGF immunophenotypes with other prognostic markers as potential biomarkers of atherosclerosis prognosis and treatment efficacy.
Methods: We performed a systematic review of the current literature to explore the role of HIF-1α and VEGF protein expression along with the relation to the prognosis and therapeutic strategies of atherosclerosis.
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