ArticleOncotarget2015
Inhibition of PI3K/AKT/mTOR axis disrupts oxidative stress-mediated survival of melanoma cells.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- The dual role of Nrf2 in melanoma: a systematic review.BMC molecular and cell biology · 2023Pooled it
- Supraphysiological 25-Hydroxyvitamin DFASEB bioAdvances · 2026Article
- Metabolic Responses of Melanocytes and Melanoma Cells to UVA Radiation and Phytocannabinoids Exposure.Antioxidants (Basel, Switzerland) · 2026Article
- Fibrosis suppressive effect and mechanism of CaSR positive allosteric modulators/p-dioxanone copolymers.Drug delivery and translational research · 2026Article
- Palmatine ameliorates MASLD in type 2 diabetes by modulating hepatic apoptosis and inflammation.Scientific reports · 2026Article
- Loss of PIK3CA AllowsCells · 2026Article
- Exercise and Phellodendron amurense extract differentially impinge on oxidative stress response pathways in a mouse model of prostate cancer.Scientific reports · 2026Article
- Loss of PIK3CA allowsbioRxiv : the preprint server for biology · 2026Article
- ENO1 Knockdown Impedes Tumour Progression and Promotes Oxidative Phosphorylation in Cutaneous Squamous Cell Carcinoma.Acta dermato-venereologica · 2025Article
- Studies on the Critical Therapeutic Role of Artemisinin and its Derivatives in Melanoma: a Review of Preclinical Evidence.Current treatment options in oncology · 2025Review
- EGF receptor in organ development, tissue homeostasis and regeneration.Journal of biomedical science · 2025Review
- Coronary Microvascular Dysfunction Is Associated With Augmented Lysosomal Signaling in Hypercholesterolemic Mice.Journal of the American Heart Association · 2024Article
- miRNAs Involvement in Modulating Signalling Pathways Involved in Ros-Mediated Oxidative Stress in Melanoma.Antioxidants (Basel, Switzerland) · 2024Review
- Coronary Microvascular Dysfunction is Associated with Augmented Lysosomal Signaling in Hypercholesterolemic Mice.bioRxiv : the preprint server for biology · 2024Article
- Vitamin C Alleviates the Negative Effects of Heat Stress on Reproductive Processes by Regulating Amino Acid Metabolism in Granulosa Cells.Antioxidants (Basel, Switzerland) · 2024Article
- Mechanism of anticancer effect of ETP-45658, a PI3K/AKT/mTOR pathway inhibitor on HT-29 Cells.Medical oncology (Northwood, London, England) · 2023Article
- SPI1 involvement in malignant melanoma pathogenesis by regulation of HK2 through the AKT1/mTOR pathway.Journal of cellular and molecular medicine · 2023Article
- A Th17 cell-intrinsic glutathione/mitochondrial-IL-22 axis protects against intestinal inflammation.bioRxiv : the preprint server for biology · 2023Article
- Interaction between moxifloxacin and Mcl-1 and MITF proteins: the effect on growth inhibition and apoptosis in MDA-MB-231 human triple-negative breast cancer cells.Pharmacological reports : PR · 2022Article
- The Impact of Oxidative Stress and AKT Pathway on Cancer Cell Functions and Its Application to Natural Products.Antioxidants (Basel, Switzerland) · 2022Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Elevated oxidative stress in cancer cells contributes to hyperactive proliferation and enhanced survival, which can be exploited using agents that increase reactive oxygen species (ROS) beyond a threshold level. Here we show that melanoma cells exhibit an oxidative stress phenotype compared with normal melanocytes, as evidenced by increased total cellular ROS, KEAP1/NRF2 pathway activity, protein damage, and elevated oxidized glutathione. Our overall objective was to test whether augmenting this high oxidative stress level in melanoma cells would inhibit their dependence on oncogenic PI3K/AKT/mTOR-mediated survival. We report that NexrutineR augmented the constitutively elevated oxidative stress markers in melanoma cells, which was abrogated by N-acetyl cysteine (NAC) pre-treatment. NexrutineR disrupted growth homeostasis by inhibiting proliferation, survival, and colony formation in melanoma cells without affecting melanocyte cell viability. Increased oxidative stress in melanoma cells inhibited PI3K/AKT/mTOR pathway through disruption of mTORC1 formation and phosphorylation of downstream targets p70S6K, 4EBP1 and rpS6. NAC pre-treatment reversed inhibition of mTORC1 targets, demonstrating a ROS-dependent mechanism. Overall, our results illustrate the importance of disruption of the intrinsically high oxidative stress in melanoma cells to selectively inhibit their survival mediated by PI3K/AKT/mTOR.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.