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Updated: Feb 9, 2026

A Tailored HPLC Purification Protocol That Yields High-purity Amyloid Beta 42 and Amyloid Beta 40 Peptides, Capable of Oligomer Formation
Published on: March 27, 2017
Amyloid-beta Interactions with ABC Transporters and Resistance Modifiers
Joseph Molnar1, Imre Ocsovszki2, Rozalia Pusztai3
1Department of Medical Microbiology and Immunobiology, University of Szeged, Szeged, Hungary molnar.jozsef@med.u-szeged.hu.
Background/Aim:
Failure of cancer chemotherapy caused by multidrug resistance (MDR) of tumor cells is mediated by ABC transporters that reduce the uptake of cytotoxic agents. Similar transporters are responsible for amyloid clearance in nerve cells in Alzheimer's disease (AD). The aim of this study was to compare the biological effects of amyloid complexes of some known ABC transporter inhibitors e.g. disiloxanes. One of the most active fragments of the pathological "endogen" substrate responsible for AD was investigated in the presence of amyloid-beta fragment on the reversal of multidrug resistance and apoptosis induction on multidrug-resistant tumor cells in model experiments.
Materials And Methods:
The efflux pump activity of the cells treated with amyloid-beta complexes was studied by Rhodamin-123 accumulation. Apoptosis induction was measured by staining of treated cells by Annexin-V and propidium iodine. The fluorescent activity FL-1 and FL-2 of the cells was measured and analyzed on a PARTEC FACScan instrument.
Results:
The resistance modifiers: disiloxanes and memantine complexed with amyloid-beta 1-42 reduced the activity of ABC transporter in MDR tumor cells. Early apoptosis was moderately increased by amyloid-beta complexes. Late apoptosis and the number of total viable cells were not changed.
Conclusion:
Amyloid-beta and its complexes inactivate the efflux pump of tumor cells resulting in accumulation of amyloid. It is supposed that reduced membrane transport can explain the lower incidence of cancer in AD.
Insights
Amyloid-beta complexes with ABC transporter inhibitors reduced multidrug resistance in tumor cells by inhibiting efflux pumps. This suggests a potential link between reduced membrane transport and lower cancer incidence in Alzheimer's disease.
Area of Science:
- Biochemistry
- Oncology
- Neuroscience
Background:
- Multidrug resistance (MDR) in cancer is mediated by ATP-binding cassette (ABC) transporters, hindering chemotherapy efficacy.
- Similar ABC transporters are involved in clearing amyloid deposits in Alzheimer's disease (AD).
Purpose of the Study:
- To investigate the effects of amyloid-beta complexes with ABC transporter inhibitors on MDR tumor cells.
- To assess the potential of these complexes in reversing multidrug resistance and inducing apoptosis.
Main Methods:
- Rhodamine-123 accumulation was used to measure efflux pump activity in treated MDR cells.
- Annexin-V and propidium iodide staining assessed apoptosis induction.
- Flow cytometry (PARTEC FACScan) analyzed cellular fluorescence.
Main Results:
- Disiloxanes and memantine complexed with amyloid-beta 1-42 decreased ABC transporter activity in MDR tumor cells.
- Amyloid-beta complexes moderately increased early apoptosis.
- No significant changes were observed in late apoptosis or total viable cell count.
Conclusions:
- Amyloid-beta and its complexes inactivate tumor cell efflux pumps, leading to amyloid accumulation.
- Reduced membrane transport activity may contribute to the observed lower cancer incidence in Alzheimer's disease patients.
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