Article ; Online: Evaluation of ABT-751, a novel anti-mitotic agent able to overcome multi-drug resistance, in melanoma cells.
Cancer chemotherapy and pharmacology
2024 Volume 93, Issue 5, Page(s) 427–437
Abstract: Purpose: Drug efflux transporter associated multi-drug resistance (MDR) is a potential limitation in the use of taxane chemotherapies for the treatment of metastatic melanoma. ABT-751 is an orally bioavailable microtubule-binding agent capable of ... ...
Abstract | Purpose: Drug efflux transporter associated multi-drug resistance (MDR) is a potential limitation in the use of taxane chemotherapies for the treatment of metastatic melanoma. ABT-751 is an orally bioavailable microtubule-binding agent capable of overcoming MDR and proposed as an alternative to taxane-based therapies. Methods: This study compares ABT-751 to taxanes in vitro, utilizing seven melanoma cell line models, publicly available gene expression and drug sensitivity databases, a lung cancer cell line model of MDR drug efflux transporter overexpression (DLKP-A), and drug efflux transporter ATPase assays. Results: Melanoma cell lines exhibit a low but variable protein and RNA expression of drug efflux transporters P-gp, BCRP, and MDR3. Expression of P-gp and MDR3 correlates with sensitivity to taxanes, but not to ABT-751. The anti-proliferative IC Conclusion: Our study confirms that ABT-751 is active against melanoma cell lines and models of MDR at physiologically relevant concentrations, it inhibits P-gp ATPase activity, and it may be a BCRP and/or MDR3 substrate. ABT-751 warrants further investigation alone or in tandem with other drug efflux transporter inhibitors for hard-to-treat MDR melanoma. |
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MeSH term(s) | Humans ; Melanoma/drug therapy ; Melanoma/pathology ; Melanoma/genetics ; Melanoma/metabolism ; Drug Resistance, Neoplasm/drug effects ; Sulfonamides/pharmacology ; Cell Line, Tumor ; Drug Resistance, Multiple/drug effects ; Taxoids/pharmacology ; Cell Proliferation/drug effects ; Antimitotic Agents/pharmacology ; Antineoplastic Agents/pharmacology ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics ; ATP Binding Cassette Transporter, Subfamily G, Member 2/metabolism ; ATP Binding Cassette Transporter, Subfamily G, Member 2/antagonists & inhibitors |
Chemical Substances | Sulfonamides ; ABT751 ; Taxoids ; Antimitotic Agents ; Antineoplastic Agents ; ATP Binding Cassette Transporter, Subfamily G, Member 2 |
Language | English |
Publishing date | 2024-01-16 |
Publishing country | Germany |
Document type | Journal Article ; Research Support, Non-U.S. Gov't |
ZDB-ID | 6820-2 |
ISSN | 1432-0843 ; 0344-5704 ; 0943-9404 |
ISSN (online) | 1432-0843 |
ISSN | 0344-5704 ; 0943-9404 |
DOI | 10.1007/s00280-023-04624-6 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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