In:
Recent Patents on Anti-Cancer Drug Discovery, Bentham Science Publishers Ltd., Vol. 17, No. 4 ( 2022-11), p. 387-395
Abstract:
Therapeutic resistance is a frequent problem of cancer treatment and a
leading cause of mortality in patients with metastatic colorectal cancer (CRC). Recent insight into the mechanisms that confer multidrug resistance has elucidated that the ATP-binding cassette (ABC) superfamily G member 2 (ABCG2) assists cancer cells in escaping therapeutic stress
caused by toxic chemotherapy. Therefore, it is necessary to develop ABCG2 inhibitors. Objective: In the present study, we investigated the inhibitory effect of KU55933 on ABCG2 in
CRC. Methods: The cytotoxicity assay and drug accumulation assay were used to examine the inhibitory
effect of KU55933 on ABCG2. The protein expressions were detected by Western blot assay. The docking assay was performed to predict the binding site and intermolecular interactions between
KU55933 and ABCG2. Results: KU55933 was more potent than the known ABCG2 inhibitor fumitremorgin C to enhance
the sensitivity of mitoxantrone and doxorubicin and the intracellular accumulation of mitoxantrone, doxorubicin and rhodamine 123 inside CRC cells with ABCG2 overexpression. Moreover,
KU55933 did not affect the protein level of ABCG2. Furthermore, the docking data showed that KU55933 was tightly located in the drug-binding pocket of ABCG2. Conclusion: KU55933 can potently inhibit the activity of ABCG2 in CRC.
Type of Medium:
Online Resource
ISSN:
1574-8928
DOI:
10.2174/1574892817666220112100036
Language:
English
Publisher:
Bentham Science Publishers Ltd.
Publication Date:
2022
