Elevated Levels of Cholesterol-Rich Lipid Rafts in Cancer Cells Are Correlated with Apoptosis Sensitivity Induced by Cholesterol-Depleting Agents
Open accessAbstract
Lipid rafts/caveolae are membrane platforms for signaling molecules that regulate various cellular functions, including cell survival. To better understand the role of rafts in tumor progression and therapeutics, we investigated the effect of raft disruption on cell viability and compared raft levels in human cancer cell lines versus their normal counterparts. Here, we report that cholesterol depletion using methyl-beta cyclodextrin caused anoikis-like apoptosis, which in A431 cells involved decreased raft levels, Bcl-xL down-regulation, caspase-3 activation, and Akt inactivation regardless of epidermal growth factor receptor activation. Cholesterol repletion replenished rafts on the cell surface and restored Akt activation and cell viability. Moreover, the breast cancer and the prostate cancer cell lines contained more lipid rafts and were more sensitive to cholesterol depletion-induced cell death than their normal counterparts. These results indicate that cancer cells contain increased levels of rafts and suggest a potential use of raft-modulating agents as anti-cancer drugs.
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Cholesterol deprivation can inhibit tumor growth, decrease phosphorylation of AKT, promote apoptosis, decrease Bcl-xl, downregulate caspase 3 activation, or hinder entry of cells into S phase.
“cholesterol deprivation can inhibit tumor growth, decrease the phosphorylation of AKT, promote apoptosis62, decrease Bcl-xl, downregulate caspase 3 activation63, or hinder entry of cells into the S phase64.”
From RETRACTED ARTICLE: Fasting inhibits aerobic glycolysis and proliferation in colorectal cancer via the Fdft1-mediated AKT/mTOR/HIF1α pathway suppression (2020) · cites this paper as [63]
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- Authors
- Li, Y. C., Park, M. J., Ye, S.-K., Kim, C.-W., & Kim, Y.-N.
- Affiliations
- Seoul National University (KR)
- Corresponding author
- Kim, Yong-Nyun
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2006-04
- Volume
- 168
- Issue
- 4
- Pages
- 1107-1118
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC1606567
- OpenAlex
- W2051818991
- Cited by
- 536
- References
- 64
- Citations by year
- 2026: 7 · 2025: 18 · 2024: 26 · 2023: 26 · 2022: 32 · 2021: 37 · 2020: 43 · 2019: 31 · 2018: 37 · 2017: 26 · 2016: 28 · 2015: 27 · 2014: 31 · 2013: 34 · 2012: 22
- FWCI
- 8.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- Korea Science and Engineering Foundation (C00524)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- lipid rafts, caveolae, cholesterol depletion, methyl-β-cyclodextrin, apoptosis, anoikis, Bcl-xL, caspase-3, Akt signaling, epidermal growth factor receptor, A431 cells, breast cancer, prostate cancer, cancer cell lines
- MeSH terms
- Breast Neoplasms, Carcinoma, Squamous Cell, Cell Survival, Cholesterol, Enzyme Activation, Female, Humans, Male, Neoplasms, Prostatic Neoplasms, Signal Transduction, Down-Regulation, Apoptosis, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Simvastatin, Caspases, Membrane Microdomains, Cell Line, Tumor, beta-Cyclodextrins, bcl-X Protein, Proto-Oncogene Proteins c-akt, Caspase 3, ErbB Receptors
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