Roles of breast cancer resistance protein and organic anion transporting polypeptide 2B1 in gastrointestinal toxicity induced by SN-38 under inflammatory conditions
Copyright © 2024 Elsevier B.V. All rights reserved..
Drug transporters are among the factors that determine the pharmacokinetic profiles after drug administration. In this study, we investigated the roles of drug transporters involved in transport of SN-38, which is an active metabolite of irinotecan, in the intestine under inflammatory conditions in vitro and determined their functional consequences. The expression alterations of breast cancer resistance protein (BCRP) and organic anion transporting polypeptide (OATP) 2B1 were determined at the mRNA and protein levels, and the subsequent functional alterations were evaluated via an accumulation study with the representative transporter substrates [prazosin and dibromofluorescein (DBF)] and SN-38. We also determined the cytotoxicity of SN-38 under inflammatory conditions. Decreased BCRP expression and increased OATP2B1 expression were observed under inflammatory conditions in vitro, which led to altered accumulation profiles of prazosin, DBF, and SN-38, and the subsequent cytotoxic profiles of SN-38. Treatment with rifampin or novobiocin supported the significant roles of BCRP and OATP2B1 in the transport and cytotoxic profile of SN-38. Collectively, these results suggest that BCRP and OATP2B1 are involved in the increased cytotoxicity of SN-38 under inflammatory conditions in vitro. Further comprehensive research is warranted to completely understand SN-38-induced gastrointestinal cytotoxicity and aid in the successful treatment of cancer with irinotecan.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:394 |
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| Enthalten in: |
Toxicology letters - 394(2024) vom: 28. Apr., Seite 57-65 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gulnaz, Aneela [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 01.04.2024 Date Revised 01.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.toxlet.2024.02.011 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Copyright © 2024 Elsevier B.V. All rights reserved. | ||
| 520 | |a Drug transporters are among the factors that determine the pharmacokinetic profiles after drug administration. In this study, we investigated the roles of drug transporters involved in transport of SN-38, which is an active metabolite of irinotecan, in the intestine under inflammatory conditions in vitro and determined their functional consequences. The expression alterations of breast cancer resistance protein (BCRP) and organic anion transporting polypeptide (OATP) 2B1 were determined at the mRNA and protein levels, and the subsequent functional alterations were evaluated via an accumulation study with the representative transporter substrates [prazosin and dibromofluorescein (DBF)] and SN-38. We also determined the cytotoxicity of SN-38 under inflammatory conditions. Decreased BCRP expression and increased OATP2B1 expression were observed under inflammatory conditions in vitro, which led to altered accumulation profiles of prazosin, DBF, and SN-38, and the subsequent cytotoxic profiles of SN-38. Treatment with rifampin or novobiocin supported the significant roles of BCRP and OATP2B1 in the transport and cytotoxic profile of SN-38. Collectively, these results suggest that BCRP and OATP2B1 are involved in the increased cytotoxicity of SN-38 under inflammatory conditions in vitro. Further comprehensive research is warranted to completely understand SN-38-induced gastrointestinal cytotoxicity and aid in the successful treatment of cancer with irinotecan | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Breast cancer resistance protein (BCRP) | |
| 650 | 4 | |a Cancer | |
| 650 | 4 | |a Irinotecan | |
| 650 | 4 | |a Organic anion transporting polypeptide (OATP) 2B1 | |
| 650 | 4 | |a SN-38 | |
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| 650 | 7 | |a ATP Binding Cassette Transporter, Subfamily G, Member 2 |2 NLM | |
| 650 | 7 | |a Neoplasm Proteins |2 NLM | |
| 650 | 7 | |a Organic Anion Transporters |2 NLM | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a Membrane Transport Proteins |2 NLM | |
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| 700 | 1 | |a Lee, Kyeong-Ryoon |e verfasserin |4 aut | |
| 700 | 1 | |a Kang, Min-Ji |e verfasserin |4 aut | |
| 700 | 1 | |a Chang, Ji-Eun |e verfasserin |4 aut | |
| 700 | 1 | |a Chae, Yoon-Jee |e verfasserin |4 aut | |
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