Cited by 688Natural product bioactivities and synthesisPhytochemical Studies and BioactivitiesPhytochemical compounds biological activities

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Betulin Is a Potent Anti-Tumor Agent that Is Enhanced by Cholesterol

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Mullauer, Franziska B., Kessler, Jan H., Medema, Jan Paul·2009·PLoS ONE

DOI 10.1371/journal.pone.0005361PMC PMC2671171

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Abstract

Betulinic Acid (BetA) and its derivatives have been extensively studied in the past for their anti-tumor effects, but relatively little is known about its precursor Betulin (BE). We found that BE induces apoptosis utilizing a similar mechanism as BetA and is prevented by cyclosporin A (CsA). BE induces cell death more rapidly as compared to BetA, but to achieve similar amounts of cell death a considerably higher concentration of BE is needed. Interestingly, we observed that cholesterol sensitized cells to BE-induced apoptosis, while there was no effect of cholesterol when combined with BetA. Despite the significantly enhanced cytotoxicity, the mode of cell death was not changed as CsA completely abrogated cell death. These results indicate that BE has potent anti-tumor activity especially in combination with cholesterol.

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Authors: Mullauer, F. B., Kessler, J. H., & Medema, J. P.
Affiliations: Amsterdam UMC Location University of Amsterdam (NL)
Leiden University Medical Center (NL)
Corresponding author: Medema, Jan Paul
ORCID: Medema, Jan Paul
Venue: PLoS ONE
Publisher: Public Library of Science (PLoS)
Published: 2009-04-28
Volume: 4
Issue: 4
Pages: e1
ISSN: 1932-6203 (ISSN-L)
DOI: 10.1371/journal.pone.0005361
PMC: PMC2671171
OpenAlex: W2168735820
Cited by: 688
References: 39
Citations by year: 2026: 7 · 2025: 23 · 2024: 25 · 2023: 30 · 2022: 29 · 2021: 55 · 2020: 35 · 2019: 29 · 2018: 37 · 2017: 34 · 2016: 45 · 2015: 39 · 2014: 43 · 2013: 55 · 2012: 55
FWCI: 26.95
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: PLoS ONE (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
UvA-DARE (University of Amsterdam) (submittedVersion, other-oa)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Pure Amsterdam UMC (submittedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Funders: Nationaal Fonds tegen Kanker
Topics: Physical Sciences › Chemistry › Organic Chemistry › Natural product bioactivities and synthesis
Physical Sciences › Chemistry › Organic Chemistry › Phytochemical Studies and Bioactivities
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Phytochemical compounds biological activities
Keywords: betulin, betulinic acid, cholesterol, apoptosis, anticancer activity, cyclosporine, cytotoxicity, combination therapy, cell death
MeSH terms: Betulinic Acid, Animals, Antineoplastic Agents, Phytogenic, Cell Line, Cells, Cultured, Cholesterol, Drug Synergism, HeLa Cells, Humans, Triterpenes, Gene Expression, Cyclosporine, Apoptosis, Reactive Oxygen Species, Mice, Knockout, Jurkat Cells, Genes, bcl-2, bcl-2 Homologous Antagonist-Killer Protein, bcl-2-Associated X Protein, Mice, Fas-Associated Death Domain Protein, Pentacyclic Triterpenes

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Betulin Is a Potent Anti-Tumor Agent that Is Enhanced by Cholesterol

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