Diterpenoid anthraquinones as chemopreventive agents altered microRNA and transcriptome expressions in cancer cells.

Biomed Pharmacother

Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, 110301, Taiwan; Department of Pharmacology, School of Medicine, College of Medicine, Tzu Chi University, Hualien, 970374, Taiwan; Department of Pharmacy, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, 427213, Taiwan. Electronic address:

Published: April 2021

AI Article Synopsis

  • The study focused on the effects of two compounds, Cryptotanshinone (CPT) and dihydrotanshinone (DHT), from traditional Chinese medicine on cell signaling pathways via changes in microRNA (miRNA).
  • Researchers found that both CPT and DHT influence cell proliferation and apoptosis by altering specific miRNAs, with DHT showing potentially stronger effects than CPT in terms of regulating these pathways.
  • The conclusion suggests that DHT is a promising candidate for cancer prevention due to its potency and lower toxicity compared to CPT, highlighting its potential role in natural medicine.

Article 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.

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http://dx.doi.org/10.1016/j.biopha.2021.111260DOI Listing

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