Evidence map›Paper›PMID 22817326›Full record

ArticleMolecular pharmaceutics2012

Epigenetic modulation of the biophysical properties of drug-resistant cell lipids to restore drug transport and endocytic functions.

Sivakumar Vijayaraghavalu, Chiranjeevi Peetla, Shan Lu, Vinod Labhasetwar

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular pharmaceutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

26 citing papers in PubMed, 79 citations in OpenAlex.

  1. Review
  2. Understanding and overcoming multidrug resistance in cancer.Nature reviews. Clinical oncology · 2025
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  5. Multifunctional Nanomaterials Mediate Cholesterol Depletion for Cancer Treatment.Angewandte Chemie (International ed. in English) · 2024
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  10. Novel Hybrid CHC from β-carboline andFrontiers in pharmacology · 2020
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  17. Review
  18. Nanomedicine of synergistic drug combinations for cancer therapy - Strategies and perspectives.Journal of controlled release : official journal of the Controlled Release Society · 2016
    Review
  19. Review
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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

4 authors at 1 institution in 1 country.

Sivakumar VijayaraghavaluDepartment of Biomedical Engineering, Lerner Research Institute, Cleveland, Ohio 44195, United States.
Chiranjeevi Peetla
Shan Lu
Vinod Labhasetwar
Cleveland Clinic Lerner College of Medicine · US

Funding

Drug Resistance In Cancer TherapyR01CA149359 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI LABHASETWAR, VINOD D · 2010 to 2014
$2.0M
NCI NIH HHS R01 CA149359NCI NIH HHS R01 CA149359-01
6 · The paper itself

Abstract

In our recent studies exploring the biophysical characteristics of resistant cell lipids, and the role they play in drug transport, we demonstrated the difference of drug-resistant breast cancer cells from drug-sensitive cells in lipid composition and biophysical properties, suggesting that cancer cells acquire a drug-resistant phenotype through the alteration of lipid synthesis to inhibit intracellular drug transport to protect from cytotoxic effect. In cancer cells, epigenetic changes (e.g., DNA hypermethylation) are essential to maintain this drug-resistant phenotype. Thus, altered lipid synthesis may be linked to epigenetic mechanisms of drug resistance. We hypothesize that reversing DNA hypermethylation in resistant cells with an epigenetic drug could alter lipid synthesis, changing the cell membrane's biophysical properties to facilitate drug delivery to overcome drug resistance. Herein we show that treating drug-resistant breast cancer cells (MCF-7/ADR) with the epigenetic drug 5-aza-2'-deoxycytidine (decitabine) significantly alters cell lipid composition and biophysical properties, causing the resistant cells to acquire biophysical characteristics similar to those of sensitive cell (MCF-7) lipids. Following decitabine treatment, resistant cells demonstrated increased sphingomyelinase activity, resulting in a decreased sphingomyelin level that influenced lipid domain structures, increased membrane fluidity, and reduced P-glycoprotein expression. Changes in the biophysical characteristics of resistant cell lipids facilitated doxorubicin transport and restored endocytic function for drug delivery with a lipid-encapsulated form of doxorubicin, enhancing the drug efficacy. In conclusion, we have established a new mechanism for efficacy of an epigenetic drug, mediated through changes in lipid composition and biophysical properties, in reversing cancer drug resistance.

Indexed as

Antineoplastic AgentsATP Binding Cassette Transporter, Subfamily B, Member 1AzacitidineBiological TransportBreast NeoplasmsCell MembraneDecitabineDNA MethylationDoxorubicinDrug Delivery SystemsDrug Resistance, NeoplasmEndocytosisEpigenesis, GeneticEpigenomicsFemaleHumansAntineoplastic AgentsATP Binding Cassette Transporter, Subfamily B, Member 1AzacitidineDecitabineDoxorubicin

Identifiers

PMID22817326
PMCPMC3433581
OpenAlexW1993899197

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.