1. Diterpenoid anthraquinones as chemopreventive agents altered microRNA and transcriptome expressions in cancer cells.
- Author
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Su YS, Kuo MZ, Kuo YT, Huang SW, Lee CJ, Su ZY, Ni YH, Li DK, and Wu TY
- Subjects
- Apoptosis drug effects, Apoptosis Regulatory Proteins genetics, Apoptosis Regulatory Proteins metabolism, Cell Cycle Proteins genetics, Cell Cycle Proteins metabolism, Cell Proliferation drug effects, Colonic Neoplasms genetics, Colonic Neoplasms metabolism, Colonic Neoplasms pathology, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, HT29 Cells, Hep G2 Cells, Humans, Liver Neoplasms genetics, Liver Neoplasms metabolism, Liver Neoplasms pathology, MicroRNAs genetics, Signal Transduction, Transcription Factors genetics, Transcription Factors metabolism, Anticarcinogenic Agents pharmacology, Antineoplastic Agents, Phytogenic pharmacology, Colonic Neoplasms drug therapy, Furans pharmacology, Liver Neoplasms drug therapy, MicroRNAs metabolism, Phenanthrenes pharmacology, Quinones pharmacology, Transcriptome drug effects
- Abstract
Objective: Cryptotanshinone (CPT) and dihydrotanshinone (DHT) are diterpenoid anthraquinone compounds extracted from traditional Chinese herbal medicine (TCM). Recent studies have shown that CPT regulates the signal transduction pathways via microRNA (miRNA) alterations. However, few studies have investigated the role of DHT in miRNA alterations affecting cell-signaling pathways. This study aimed to investigate the miRNA alterations and post-transcriptional regulation activities of DHT in comparison to CPT., Methods: HepG2 and HT-29 cells were treated with DHT or CPT for 72 h. MiRNA, transcription factor encoding mRNA, and downstream gene expression were determined using real-time quantitative PCR. Protein expression was analyzed using western blotting., Results: The results revealed that CPT and DHT targeted cell proliferation and apoptosis signaling pathways via miR-15a-5p, miR-27a-5p, miR-100-5p, and miR-200a-5p alterations.In silico target predictions showed that downregulation of epidermal growth factor receptor (EGFR) mRNA expression by DHT might also suppress the expression of STAT family proteins and lead to anti-proliferation effects. We also found that, compared to CPT, DHT might possess higher potency in cell growth regulation via multi-miRNA and transcription factor alterations., Conclusion: This study revealed that CPT and DHT targeted cell proliferation and apoptosis signaling pathways via alterations in miRNAs and transcription factors. In addition, the findings of this study suggest that DHT is more potent than CPT in cancer chemopreventive activities. Therefore, DHT at a low dose is a TCM compound with less toxic side effects and may contribute to the development of natural medicine as a potential cancer chemopreventive agent., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Published
- 2021
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