PUBLICATION
Probing Synergistic Targets by Natural Compounds for Hepatocellular Carcinoma
- Authors
- Gao, J., Yin, Z., Wu, Z., Sheng, Z., Ma, C., Chen, R., Zhang, X., Tang, K., Fei, J., Cao, Z.
- ID
- ZDB-PUB-210817-6
- Date
- 2021
- Source
- Frontiers in cell and developmental biology 9: 715762 (Journal)
- Registered Authors
- Keywords
- cancer system biology, drug discovery, hepatocellular carcinoma, natural compounds, synergistic targets
- MeSH Terms
- none
- PubMed
- 34395446 Full text @ Front Cell Dev Biol
Citation
Gao, J., Yin, Z., Wu, Z., Sheng, Z., Ma, C., Chen, R., Zhang, X., Tang, K., Fei, J., Cao, Z. (2021) Probing Synergistic Targets by Natural Compounds for Hepatocellular Carcinoma. Frontiers in cell and developmental biology. 9:715762.
Abstract
Background Designing combination drugs for malignant cancers has been restricted due to the scarcity of synergy-medicated targets, while some natural compounds have demonstrated potential to enhance anticancer effects.
Methods We here explored the feasibility of probing synergy-mediated targets by Berberine (BER) and Evodiamine (EVO) in hepatocellular carcinoma (HCC). Using the genomics-derived HCC signaling networks of compound treatment, NF-κB and c-JUN were inferred as key responding elements with transcriptional activity coinhibited during the synergistic cytotoxicity induction in BEL-7402 cells. Then, selective coinhibitors of NF-κB and c-JUN were tested demonstrating similar synergistic antiproliferation activity.
Results Consistent with in vivo experiments of zebrafish, coinhibitors were found to significantly reduce tumor growth by 79% and metastasis by 96% compared to blank control, accompanied by anti-angiogenic activity. In an analysis of 365 HCC individuals, the low expression group showed significantly lower malignancies and better prognosis, with the median survival time increased from 67 to 213%, compared to the rest of the groups.
Conclusion Together, NF-κB and c-JUN were identified as promising synergistic inducers in developing anti-HCC therapies. Also, our method may provide a feasible strategy to explore new targeting space from natural compounds, opening opportunities for the rational design of combinational formulations in combatting malignant cancers.
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Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping