The Genotoxic and Pro-Apoptotic Activities of Advanced Glycation End-Products (MAGE) Measured with Micronuclei Assay Are Inhibited by Their Low Molecular Mass Counterparts
An association between the cancer invasive activities of cells and their exposure to advanced glycation end-products (AGEs) was described early in some reports. An incubation of cells with BSA-AGE (bovine serum albumin-AGE), BSA-carboxymethyllysine and BSA-methylglyoxal (BSA-MG) resulted in a significant increase in DNA damage. We examined the genotoxic activity of new products synthesized under nonaqueous conditions. These were high molecular mass MAGEs (HMW-MAGEs) formed from protein and melibiose and low molecular mass MAGEs (LMW-MAGEs) obtained from the melibiose and N-α-acetyllysine and N-α-acetylarginine. We have observed by measuring of micronuclei in human lymphocytes in vitro that the studied HMW-MAGEs expressed the genotoxicity. The number of micronuclei (MN) in lymphocytes reached 40.22 ± 5.34 promille (MN/1000CBL), compared to 28.80 ± 6.50 MN/1000 CBL for the reference BSA-MG, whereas a control value was 20.66 ± 1.39 MN/1000CBL. However, the LMW-MAGE fractions did not induce micronuclei formation in the culture of lymphocytes and partially protected DNA against damage in the cells irradiated with X-ray. Human melanoma and all other studied cells, such as bronchial epithelial cells, lung cancer cells and colorectal cancer cells, are susceptible to the genotoxic effects of HMW-MAGEs. The LMW-MAGEs are not genotoxic, while they inhibit HMW-MAGE genotoxic activity. With regard to apoptosis, it is induced with the HMW-MAGE compounds, in the p53 independent way, whereas the low molecular mass product inhibits the apoptosis induction. Further investigations will potentially indicate beneficial apoptotic effect on cancer cells.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2021 |
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Erschienen: |
2021 |
Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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Enthalten in: |
Genes - 12(2021), 5 vom: 13. Mai |
Sprache: |
Englisch |
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Beteiligte Personen: |
Czech, Monika [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 23.08.2021 Date Revised 23.08.2021 published: Electronic Citation Status MEDLINE |
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doi: |
10.3390/genes12050729 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM326166203 |
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520 | |a An association between the cancer invasive activities of cells and their exposure to advanced glycation end-products (AGEs) was described early in some reports. An incubation of cells with BSA-AGE (bovine serum albumin-AGE), BSA-carboxymethyllysine and BSA-methylglyoxal (BSA-MG) resulted in a significant increase in DNA damage. We examined the genotoxic activity of new products synthesized under nonaqueous conditions. These were high molecular mass MAGEs (HMW-MAGEs) formed from protein and melibiose and low molecular mass MAGEs (LMW-MAGEs) obtained from the melibiose and N-α-acetyllysine and N-α-acetylarginine. We have observed by measuring of micronuclei in human lymphocytes in vitro that the studied HMW-MAGEs expressed the genotoxicity. The number of micronuclei (MN) in lymphocytes reached 40.22 ± 5.34 promille (MN/1000CBL), compared to 28.80 ± 6.50 MN/1000 CBL for the reference BSA-MG, whereas a control value was 20.66 ± 1.39 MN/1000CBL. However, the LMW-MAGE fractions did not induce micronuclei formation in the culture of lymphocytes and partially protected DNA against damage in the cells irradiated with X-ray. Human melanoma and all other studied cells, such as bronchial epithelial cells, lung cancer cells and colorectal cancer cells, are susceptible to the genotoxic effects of HMW-MAGEs. The LMW-MAGEs are not genotoxic, while they inhibit HMW-MAGE genotoxic activity. With regard to apoptosis, it is induced with the HMW-MAGE compounds, in the p53 independent way, whereas the low molecular mass product inhibits the apoptosis induction. Further investigations will potentially indicate beneficial apoptotic effect on cancer cells | ||
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700 | 1 | |a Staniszewska, Magdalena |e verfasserin |4 aut | |
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700 | 1 | |a Witkowska, Danuta |e verfasserin |4 aut | |
700 | 1 | |a Gamian, Andrzej |e verfasserin |4 aut | |
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