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

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

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
Venue
PLoS ONE
Published
2009-04-28
Volume
4
Issue
4
Pages
e1
ISSN
1932-6203 (ISSN-L)
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
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
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Natural product bioactivities and synthesis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phytochemical Studies and Bioactivities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › 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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