ArticlePloS one2017
CC-223 blocks mTORC1/C2 activation and inhibits human hepatocellular carcinoma cells in vitro and in vivo.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 25 citations in OpenAlex.
- CC223 enhances cisplatin sensitivity of platinum-resistant ovarian cancer by inducing cell cycle arrest.Journal of ovarian research · 2026Article
- Spatiotemporal Heterogeneity of Tumor Glucose Metabolism Reprogramming: From Single-Cell Mechanisms to Precision Interventions.International journal of molecular sciences · 2025Review
- Small-molecule-based targeted therapy in liver cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Targeting mTOR signaling pathways in multiple myeloma: biology and implication for therapy.Cell communication and signaling : CCS · 2024Review
- Roles of Rictor alterations in gastrointestinal tumors (Review).Oncology reports · 2024Article
- Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease.Signal transduction and targeted therapy · 2023Review
- Identification of Promising Drug Candidates against Prostate Cancer through Computationally-Driven Drug Repurposing.International journal of molecular sciences · 2023Article
- The Role of PI3K/AKT/mTOR Signaling in Hepatocellular Carcinoma Metabolism.International journal of molecular sciences · 2023Review
- An mTOR and DNA-PK dual inhibitor CC-115 hinders non-small cell lung cancer cell growth.Cell death discovery · 2022Article
- Article
- Hepatocellular carcinoma (HCC): the most promising therapeutic targets in the preclinical arena based on tumor biology characteristics.Expert opinion on therapeutic targets · 2021Review
- Combating TKI resistance in CML by inhibiting the PI3K/Akt/mTOR pathway in combination with TKIs: a review.Medical oncology (Northwood, London, England) · 2021Review
- Role of the Mammalian Target of Rapamycin Pathway in Liver Cancer: From Molecular Genetics to Targeted Therapies.Hepatology (Baltimore, Md.) · 2021Review
- Advances of Targeted Therapy for Hepatocellular Carcinoma.Frontiers in oncology · 2021Review
- Physiopathology of the Permeability Transition Pore: Molecular Mechanisms in Human Pathology.Biomolecules · 2020Review
- The role of RICTOR amplification in targeted therapy and drug resistance.Molecular medicine (Cambridge, Mass.) · 2020Review
- Dual-Ligand Functionalized Core-Shell Chitosan-Based Nanocarrier for Hepatocellular Carcinoma-Targeted Drug Delivery.International journal of nanomedicine · 2020Article
- Targeting ROR1 inhibits epithelial to mesenchymal transition in human lung adenocarcinoma via mTOR signaling pathway.International journal of clinical and experimental pathology · 2018Article
- Jujube leaf green tea extracts inhibits hepatocellular carcinoma cells by activating AMPK.Oncotarget · 2017Article
- Kaempferol induces autophagic cell death of hepatocellular carcinoma cells via activating AMPK signaling.Oncotarget · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related human mortalities. Over-activation of mammalian target of rapamycin (mTOR) is important for HCC tumorigenesis and progression. The current study assessed the potential anti-HCC activity by a novel mTOR kinase inhibitor, CC-223. We demonstrate that CC-223, at nM concentrations, induced profound cytotoxic and anti-proliferative activities against established HCC cell lines (HepG2, KYN-2 and Huh-7) and primary human HCC cells. Meanwhile, CC-223 activated caspase-3/-9 and apoptosis in the above HCC cells. CC-223 concurrently blocked mTORC1 and mTORC2 activation, and its cytotoxicity against HCC cells was much more potent than the traditional mTORC1 inhibitors (RAD001 and rapamycin). Further studies demonstrated that CC-223 disrupted mitochondrial function, and induced mitochondrial permeability transition pore (mPTP) opening and reactive oxygen species (ROS) production. On the other hand, ROS scavengers and mPTP blockers (cyclosporin A or sanglifehrin A) largely attenuated CC-223-induced HepG2 cell apoptosis. In vivo studies showed that oral administration of CC-223 dramatically inhibited growth of HepG2 xenografts in severe combined immuno-deficient (SCID) mice. mTORC1/2 activation was also blocked in xenografts with CC-223 administration. Together, CC-223 simultaneously blocks mTORC1/2 and efficiently inhibits human HCC 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.