Dorsomorphin attenuates ABCG2-mediated multidrug resistance in colorectal cancer

Colorectal cancer is a common malignant tumor with high mortality, for which chemotherapy resistance is one of the main reasons. The high expression of ABCG2 in the cancer cells and expulsion of anticancer drugs directly cause multidrug resistance (MDR). Therefore, the development of new ABCG2 inhib...

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Published inFrontiers in pharmacology Vol. 15; p. 1393693
Main Authors Li, Xiao-Peng, Cao, Liang-Qi, Yu, Ze-Zhong, He, Ke, Ding, Peng-Bo, Li, Ji-Sheng, Shan, Yi-Yao, Su, Yu-Bin, Yuan, Zhong-Min, Shi, Zhi
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 24.05.2024
Subjects
ABCG2
chemosensitivity
colorectal cancer
dorsomorphin
multidrug resistance
Pharmacology
multidrug resistance
colorectal cancer
dorsomorphin
chemosensitivity
ABCG2
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Summary:Colorectal cancer is a common malignant tumor with high mortality, for which chemotherapy resistance is one of the main reasons. The high expression of ABCG2 in the cancer cells and expulsion of anticancer drugs directly cause multidrug resistance (MDR). Therefore, the development of new ABCG2 inhibitors that block the active causes of MDR may provide a strategy for the treatment of colorectal cancer. In this study, we find that dorsomorphin (also known as compound C or BML-275) potently inhibits the transporter activity of ABCG2, thereby preserving the chemotherapeutic agents mitoxantrone and doxorubicin to antagonize MDR in ABCG2-overexpressing colorectal cancer cells. Additionally, dorsomorphin does not alter ABCG2 protein expression. The results of molecular docking studies show that dorsomorphin is bound stably to the ABCG2-binding pocket, suggesting that dorsomorphin is a potent ABCG2 inhibitor that attenuates ABCG2-mediated MDR in colorectal cancer.
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Reviewed by: Changliang Shan, Nankai University, China
Xiaofang Guo, University of South Florida, United States
These authors have contributed equally to this work
Edited by: Hailin Tang, Sun Yat-sen University Cancer Center (SYSUCC), China
ISSN:1663-9812
1663-9812
DOI:10.3389/fphar.2024.1393693