Diterpenoid anthraquinones as chemopreventive agents altered microRNA and transcriptome expressions in cancer cells
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 in...
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2021-04-01
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doaj-3cce6b2859d14d13aeea212c5a8a6d892021-07-17T04:32:25ZengElsevierBiomedicine & Pharmacotherapy0753-33222021-04-01136111260Diterpenoid anthraquinones as chemopreventive agents altered microRNA and transcriptome expressions in cancer cellsYing-Shih Su0Min Zhan Kuo1Yi Ting Kuo2Shu-Wei Huang3Chia-Jung Lee4Zheng-Yuan Su5Yu-Hui Ni6Dian-Kun Li7Tien-Yuan Wu8School of Medicine, College of Medicine, Tzu Chi University, Hualien, 970374, Taiwan; Division of Infectious Diseases, Department of Internal Medicine, Wan Fang Medical Center, Taipei Medical University, Taipei, 116081, TaiwanSchool of Medicine, College of Medicine, Tzu Chi University, Hualien, 970374, TaiwanSchool of Medicine, College of Medicine, Tzu Chi University, Hualien, 970374, TaiwanInstitute of Preventive Medicine, National Defense Medical Center, Taipei, 114201, TaiwanCollege of Pharmacy, Taipei Medical University, Taipei, 110301, Taiwan; Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, 110301, TaiwanDepartment of Bioscience Technology, Chung Yuan Christian University, Taoyuan City, 320, TaiwanDepartment of Oncology, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, 427213, TaiwanDepartment of Oncology, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, 427213, TaiwanTraditional 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; Corresponding author at: Department of Pharmacology, School of Medicine, College of Medicine, Tzu Chi University, No. 701, Sec. 3, Zhong-Yang Road, Hualien, 970374, Taiwan.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.http://www.sciencedirect.com/science/article/pii/S0753332221000457Diterpenoid anthraquinonesTraditional Chinese herbal medicineCryptotanshinoneDihydrotanshinonemicroRNAChemoprevention |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ying-Shih Su Min Zhan Kuo Yi Ting Kuo Shu-Wei Huang Chia-Jung Lee Zheng-Yuan Su Yu-Hui Ni Dian-Kun Li Tien-Yuan Wu |
spellingShingle |
Ying-Shih Su Min Zhan Kuo Yi Ting Kuo Shu-Wei Huang Chia-Jung Lee Zheng-Yuan Su Yu-Hui Ni Dian-Kun Li Tien-Yuan Wu Diterpenoid anthraquinones as chemopreventive agents altered microRNA and transcriptome expressions in cancer cells Biomedicine & Pharmacotherapy Diterpenoid anthraquinones Traditional Chinese herbal medicine Cryptotanshinone Dihydrotanshinone microRNA Chemoprevention |
author_facet |
Ying-Shih Su Min Zhan Kuo Yi Ting Kuo Shu-Wei Huang Chia-Jung Lee Zheng-Yuan Su Yu-Hui Ni Dian-Kun Li Tien-Yuan Wu |
author_sort |
Ying-Shih Su |
title |
Diterpenoid anthraquinones as chemopreventive agents altered microRNA and transcriptome expressions in cancer cells |
title_short |
Diterpenoid anthraquinones as chemopreventive agents altered microRNA and transcriptome expressions in cancer cells |
title_full |
Diterpenoid anthraquinones as chemopreventive agents altered microRNA and transcriptome expressions in cancer cells |
title_fullStr |
Diterpenoid anthraquinones as chemopreventive agents altered microRNA and transcriptome expressions in cancer cells |
title_full_unstemmed |
Diterpenoid anthraquinones as chemopreventive agents altered microRNA and transcriptome expressions in cancer cells |
title_sort |
diterpenoid anthraquinones as chemopreventive agents altered microrna and transcriptome expressions in cancer cells |
publisher |
Elsevier |
series |
Biomedicine & Pharmacotherapy |
issn |
0753-3322 |
publishDate |
2021-04-01 |
description |
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. |
topic |
Diterpenoid anthraquinones Traditional Chinese herbal medicine Cryptotanshinone Dihydrotanshinone microRNA Chemoprevention |
url |
http://www.sciencedirect.com/science/article/pii/S0753332221000457 |
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