ArticleBiochemical pharmacology2013
7-Ketocholesterol induces P-glycoprotein through PI3K/mTOR signaling in hepatoma cells.
Article in Biochemical pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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
25 citing papers in PubMed, 56 citations in OpenAlex.
- Immune Modulatory Oxysterols Produced from Cholesterol-Containing Lipid Nanoparticles Regulate Tumor Growth.ACS nano · 2026Article
- Immunometabolic Targets in CD8Liver cancer · 2025Review
- Review
- Therapeutic Applications of Oxysterols and Derivatives in Age-Related Diseases, Infectious and Inflammatory Diseases, and Cancers.Advances in experimental medicine and biology · 2024Review
- Suppression of hepatocellular carcinoma by Ulva lactuca ulvan via gut microbiota and metabolite interactions.Journal of advanced research · 2023Article
- Effects of 7-ketocholesterol on tamoxifen efficacy in breast carcinoma cell line models in vitro.The Journal of steroid biochemistry and molecular biology · 2023Article
- Therapeutic avenues for targeting treatment challenges of diffuse midline gliomas.Neoplasia (New York, N.Y.) · 2023Review
- Reactive Sulfur Compounds in the Fight against COVID-19.Antioxidants (Basel, Switzerland) · 2022Review
- Raman spectroscopy biochemical characterisation of bladder cancer cisplatin resistance regulated by FDFT1: a review.Cellular & molecular biology letters · 2022Review
- Exosomal microRNA-107 reverses chemotherapeutic drug resistance of gastric cancer cells through HMGA2/mTOR/P-gp pathway.BMC cancer · 2021Article
- Regulation of ABC Drug Efflux Transporters in Human T-Cells Exposed to an HIV Pseudotype.Frontiers in pharmacology · 2021Article
- Cholesterol Degradation and Production of Extracellular Cholesterol Oxidase fromBioMed research international · 2019Article
- The Oxysterol 7-Ketocholesterol Reduces Zika Virus Titers in Vero Cells and Human Neurons.Viruses · 2018Article
- Article
- 7-ketocholesterol and 27-hydroxycholesterol decreased doxorubicin sensitivity in breast cancer cells: estrogenic activity and mTOR pathway.Oncotarget · 2017Article
- The down-regulation of SLC7A11 enhances ROS induced P-gp over-expression and drug resistance in MCF-7 breast cancer cells.Scientific reports · 2017Article
- 7-ketocholesterol induces apoptosis of MC3T3-E1 cells associated with reactive oxygen species generation, endoplasmic reticulum stress and caspase-3/7 dependent pathway.Molecular genetics and metabolism reports · 2017Article
- Drug Transporter Expression and Activity in Human Hepatoma HuH-7 Cells.Pharmaceutics · 2016Article
- 7-Ketocholesterol induces ATM/ATR, Chk1/Chk2, PI3K/Akt signalings, cytotoxicity and IL-8 production in endothelial cells.Oncotarget · 2016Article
- Evaluation of CYP3A4 inhibition and hepatotoxicity using DMSO-treated human hepatoma HuH-7 cells.Cell biology and toxicology · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
7-Ketocholesterol (7-KC) is found at an elevated level in patients with cancer and chronic liver disease. The up-regulation of an efflux pump, P-glycoprotein (P-gp) leads to drug resistance. To elucidate the effect of 7-KC on P-gp, P-gp function and expression were investigated in hepatoma cell lines Huh-7 and HepG2 and in primary hepatocyte-derived HuS-E/2 cells. At a subtoxic concentration, 48-h exposure to 7-KC reduced the intracellular accumulation and cytotoxicity of P-gp substrate doxorubicin in hepatoma cells, but not in HuS-E/2 cells. In Huh-7 cells, 7-KC elevated efflux function through the activation of phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway. 7-KC activated the downstream protein synthesis initiation factor 4E-BP1 and induced P-gp expression post-transcriptionally. The stimulation of efflux was reversible and could not be prevented by N-acetyl cysteine. Total cellular ATP content remained the same, whereas the lactate production was increased and fluorescence lifetime of protein-bound NADH was shortened. These changes suggested a metabolic shift to glycolysis, but glycolytic inhibitors did not eliminate 7-KC-mediated P-gp induction. These results demonstrate that 7-KC induces P-gp through PI3K/mTOR signaling and decreased the cell-killing efficacy of doxorubicin in hepatoma cells.
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.