한빛사논문
- 조회333
순천대학교 약학대학
Mücahit Varl 1, Moongi Ji 1, Eunae Kim 2, Sung Jin Kim 3, Byeongchan Choi 1, Hyung-Ho Ha 1, Kyung Keun Kim 3, Man-Jeong Paik 1, Hangun Kim 1
1College of Pharmacy, Sunchon National University, Sunchon, Republic of Korea
2College of Pharmacy, Chosun University, 146 Chosundae-gil, Gwangju 61452, Republic of Korea
3Department of Pharmacology, Chonnam National University Medical School, 160 Baekseoro, Dong-gu, Gwangju, 61469, Republic of Korea
Corresponding author : Hangun Kim
Abstract
Background
The KITENIN/ErbB4 complex has been reported to participate in metastasis, which is the principal reason of death in most colorectal cancer patients.
Purpose
New therapeutics need to be developed to suppress the malignant effects of the KITENIN/ErbB4 complex, which is related to drug resistance. The present study aimed to evaluate changes in cancer cell invasion capacity, transcriptional regulators, and cellular bioenergetics after targeting the KITENIN/ErbB4 complex with emodin. Moreover, we aimed to reveal the mechanistic effects of emodin and observe the dual blockade effects of ErbB4-targeted therapy with KH-type splicing regulatory protein (KSRP) and search for new alternative blockade pathways.
Methods
Using in vitro, in vivo, molecular-docking, and metabolomics studies, we evaluated the anticancer effect of emodin alone or in combination with DKC-C14S.
Results
Emodin treatment decreased KITENIN and ErbB4 protein levels. The dysfunctional KITENIN/ErbB4 complex suppressed KITENIN-mediated cell invasion and downregulated AP-1 activity, aerobic glycolysis, and the levels of transcriptional regulators associated with cell metabolism. We conclude that emodin targets the KITENIN/ErbB4 complex and offering a novel mechanism by which it disrupts KITENIN-mediated signaling. Furthermore, we were demonstrated that the dual blocking effect of emodin and DKC-14S on the KITENIN complex showed synergistic effects in suppressing colorectal cancer progression under in cell-based and animal assay.
Conclusion
The results suggest that co-treatment with ErbB4 and KSRP-binding compounds could constitute a potential strategy for the control colorectal cancer progression by disrupting the KITENIN complex.
논문정보
- Research article
- 2024년 11월 (BRIC 등록일 2024-11-12)
- 국내 연구진
- 의약학 > 약학
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