Evidence map›Paper›PMID 28923401›Full record

ArticleCancer letters2017

Pharmacological blockade of cholesterol trafficking by cepharanthine in endothelial cells suppresses angiogenesis and tumor growth.

Junfang Lyu, Eun Ju Yang, Sarah A Head, Nana Ai, Baoyuan Zhang, Changjie Wu, Ruo-Jing Li, Yifan Liu, Chen Yang, Yongjun Dang and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer letters, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 1 pooled it
2.8field-weighted citation impact, top 9% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

49 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Dysregulation of cholesterol homeostasis in cancer pathogenesis.Cellular and molecular life sciences : CMLS · 2025
    Review
  8. Abnormal changes in metabolites caused by mJournal of advanced research · 2025
    Review
  9. Review
  10. Article
  11. Multifunctional Nanomaterials Mediate Cholesterol Depletion for Cancer Treatment.Angewandte Chemie (International ed. in English) · 2024
    Review
  12. Upregulation of NPC1 and its association with poor prognosis in gastric cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024
    Article
  13. Article
  14. Review
  15. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 4 countries.

Junfang LyuFaculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.
Eun Ju YangFaculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.
Sarah A HeadDepartment of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; The SJ Yan and HJ Mao Laboratory of Chemical Biology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Nana AiFaculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.
Baoyuan ZhangFaculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.
Changjie WuFaculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.
Ruo-Jing LiDepartment of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; The SJ Yan and HJ Mao Laboratory of Chemical Biology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Yifan LiuFaculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.
Chen YangKey Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
Yongjun DangKey Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
Ho Jeong KwonChemical Genomics Global Research Laboratory, Department of Biotechnology, College of Life Science & Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
Wei GeFaculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.
Jun O LiuDepartment of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; The SJ Yan and HJ Mao Laboratory of Chemical Biology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Joong Sup ShimFaculty of Health Sciences, University of Macau, Taipa, Macau SAR, China; Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; The SJ Yan and HJ Mao Laboratory of Chemical Biology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA. Electronic address: jsshim@umac.mo.
University of Macau · MOJohns Hopkins University · USFudan University · CNYonsei University · KR

Funding

Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1M
Studies of the Antifungal Drug Itraconazole As A Novel Inhibitor of AngiogenesisR01CA184103 · NCI · JOHNS HOPKINS UNIVERSITY · PI LIU, JUN O. · 2015 to 2019
$1.8M
NCATS NIH HHS UL1 TR001079NCI NIH HHS R01 CA184103
6 · The paper itself

Abstract

Cholesterol is an important modulator of membrane protein function and signaling in endothelial cells, thus making it an emerging target for anti-angiogenic agents. In this study, we employed a phenotypic screen that detects intracellular cholesterol distribution in endothelial cells (HUVEC) and identified 13 existing drugs as cholesterol trafficking inhibitors. Cepharanthine, an approved drug for anti-inflammatory and cancer management use, was amongst the candidates, which was selected for in-depth mechanistic studies to link cholesterol trafficking and angiogenesis. Cepharanthine inhibited the endolysosomal trafficking of free-cholesterol and low-density lipoprotein in HUVEC by binding to Niemann-Pick disease, type C1 (NPC1) protein and increasing the lysosomal pH. The blockade of cholesterol trafficking led to a cholesterol-dependent dissociation of mTOR from the lysosomes and inhibition of its downstream signaling. Cepharanthine inhibited angiogenesis in HUVEC and in zebrafish in a cholesterol-dependent manner. Furthermore, cepharanthine suppressed tumor growth in vivo by inhibiting angiogenesis and it enhanced the antitumor activity of the standard chemotherapy cisplatin in lung and breast cancer xenografts in mice. Altogether, these results strongly support the idea that cholesterol trafficking is a viable drug target for anti-angiogenesis and that the inhibitors identified among existing drugs, such as cepharanthine, could be potential anti-angiogenic and antitumor agents.

Indexed as

Angiogenesis InhibitorsAnimalsAnimals, Genetically ModifiedAntineoplastic Agents, PhytogenicAntineoplastic Combined Chemotherapy ProtocolsBenzodioxolesBenzylisoquinolinesCell Growth ProcessesCholesterolCisplatinDrug SynergismHumansHuman Umbilical Vein Endothelial CellsLysosomesMiceMice, Inbred NODAngiogenesis InhibitorsAntineoplastic Agents, PhytogenicBenzodioxolesBenzylisoquinolinescepharanthineCholesterolCisplatinAngiogenesisCepharanthineCholesterol traffickingLysosomeTumor

Identifiers

PMID28923401
PMCPMC5634947
OpenAlexW2753956667

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.