Abstract:
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.
journal_name
Anticancer Resjournal_title
Anticancer researchauthors
Molnar J,Ocsovszki I,Pusztai Rdoi
10.21873/anticanres.12608subject
Has Abstractpub_date
2018-06-01 00:00:00pages
3407-3410issue
6eissn
0250-7005issn
1791-7530pii
38/6/3407journal_volume
38pub_type
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journal_title:Anticancer research
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journal_title:Anticancer research
pub_type: 杂志文章,评审
doi:
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journal_title:Anticancer research
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doi:
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