ArticleOncogene2003
Glutathione depletion-induced apoptosis of Ha-ras-transformed NIH3T3 cells can be prevented by melatonin.
Article in Oncogene, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 52 citations in OpenAlex.
- NPRL2 is required for proliferation of oncogenic Ras-transformed bronchial epithelial cells.Cell division · 2024Article
- Compensatory combination of romidepsin with gemcitabine and cisplatin to effectively and safely control urothelial carcinoma.British journal of cancer · 2020Article
- The Delicate Equilibrium between Oxidants and Antioxidants in Brain Glioma.Current neuropharmacology · 2019Review
- Similarities and Distinctions of Cancer and Immune Metabolism in Inflammation and Tumors.Cell metabolism · 2017Article
- Melatonin enhances sensitivity to fluorouracil in oesophageal squamous cell carcinoma through inhibition of Erk and Akt pathway.Cell death & disease · 2016Article
- A Synthetic Lethal Interaction between Glutathione Synthesis and Mitochondrial Reactive Oxygen Species Provides a Tumor-Specific Vulnerability Dependent on STAT3.Molecular and cellular biology · 2015Article
- Decreasing GSH and increasing ROS in chemosensitivity gliomas with IDH1 mutation.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Oxidative stress and the unfulfilled promises of antioxidant agents.Ecancermedicalscience · 2015Review
- An IDH1 mutation inhibits growth of glioma cells via GSH depletion and ROS generation.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2014Article
- Role of melatonin in traumatic brain injury and spinal cord injury.TheScientificWorldJournal · 2014Review
- Multifunctional Effects of Mangosteen Pericarp on Cognition in C57BL/6J and Triple Transgenic Alzheimer's Mice.Evidence-based complementary and alternative medicine : eCAM · 2014Article
- Differential induction of reactive oxygen species through Erk1/2 and Nox-1 by FK228 for selective apoptosis of oncogenic H-Ras-expressing human urinary bladder cancer J82 cells.Journal of cancer research and clinical oncology · 2011Article
- Role of reactive oxygen species in proapoptotic ability of oncogenic H-Ras to increase human bladder cancer cell susceptibility to histone deacetylase inhibitor for caspase induction.Journal of cancer research and clinical oncology · 2009Article
- Increased oxidative stress in diabetes regulates activation of a small molecular weight G-protein, H-Ras, in the retina.Molecular vision · 2007Article
- Gene expression signature of primary imatinib-resistant chronic myeloid leukemia patients.Leukemia · 2006Article
- Signaling pathways influencing SLF and c-kit-mediated survival and proliferation.Immunologic research · 2006Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It is well known that intracellular antioxidant glutathione (GSH) plays major roles in the maintenance of redox status and defense of oxidative stress. Ras, a small GTP-binding protein, may send growth-stimulating message to the nucleus through downstream Rac oncoprotein and superoxide (O(2*-)). These findings led us to investigate the effects of GSH and melatonin, a free-radical scavenger, on Ras-Rac-O(2*-)-related growth signal transduction. Our results demonstrate that overexpression of the inducible Ha-ras oncogene by isopropyl-beta-D-thiogalactoside (IPTG) increases the levels of reactive oxygen species (ROS, including O(2*-) and hydrogen peroxide (H(2)O(2))) and GSH in an Ha-ras-transformed NIH/3T3 fibroblast cell line. On the contrary, melatonin significantly suppresses ras-triggered cell growth by inhibiting the increase of ROS and GSH. Moreover, severe apoptosis of this transformed cell line occurred when the cell redox balance between ROS and GSH was dramatically changed in the presence of IPTG and L-buthionine-[S,R]-sulfoximine (BSO, a specific inhibitor of GSH synthetase). That BSO-induced cell apoptosis needs Ras to increase the ROS level was demonstrated by the free-radical scavenger melatonin. It effectively blocked cell apoptosis, but cell growth was also slowed without affecting Ras expression. Based on our studies, two approaches can be applied to treating ras-related cancers. One is utilizing melatonin to suppress cancer cell proliferation, and the other is utilizing BSO to induce cancer-cell apoptosis. Cotreatment of ras-related cancer cells with melatonin and BSO stops cell growth as well as apoptosis. Whether these cancer cells will undergo further regression or become recurrent merits investigation.
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