Inhibitory effect of flavonoid xanthomicrol on triple-negative breast tumor via regulation of cancer-associated microRNAs.


Journal

Phytotherapy research : PTR
ISSN: 1099-1573
Titre abrégé: Phytother Res
Pays: England
ID NLM: 8904486

Informations de publication

Date de publication:
Apr 2021
Historique:
revised: 12 09 2020
received: 01 05 2020
accepted: 17 10 2020
pubmed: 21 11 2020
medline: 1 5 2021
entrez: 20 11 2020
Statut: ppublish

Résumé

Breast cancer is the leading cause of cancer death in women worldwide. Due to the side effects of current chemo-reagents on healthy tissues, it is essential to search for alternative compounds with less toxicity and better efficacy. In the present study, we have investigated the anticancer effects of flavonoid xanthomicrol on the mice breast cancer model using MTT assay, cell cycle and Annexin/PI analysis, colony formation assay, H&E staining, immunohistochemistry, and miRNA analysis. Our results demonstrated that xanthomicrol decreased the cell viability and clonogenic capability, induced G1-arrest and apoptosis in the breast cancer cells in vitro, and caused a significant reduction in the volume and weight of mice tumors in vivo. In addition, xanthomicrol reduced the expression of TNFα, VEGF, MMP9, and Ki67, while upregulating the expression of apoptotic markers such as Bax, caspase3, and caspase9. Finally, the expression of miR21, miR27, and miR125, known as oncomirs, decreased significantly after xanthomicrol administration, while the expression of miR29 and miR34, functioning as tumor suppressors, increased significantly (p < .001). Our data demonstrated that xanthomicrol can induce apoptosis and suppress angiogenesis in breast cancer cells due to its inhibitory effect on oncomirs and its stimulatory effect on tumor suppressor miRNAs.

Identifiants

pubmed: 33217075
doi: 10.1002/ptr.6940
doi:

Substances chimiques

Flavones 0
Flavonoids 0
MicroRNAs 0
xanthomicrol 3IN82Y8CAA

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1967-1982

Subventions

Organisme : Iran National Science Foundation
ID : 96009946

Informations de copyright

© 2020 John Wiley & Sons Ltd.

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Auteurs

Farnoosh Attari (F)

Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran.

Faezeh Keighobadi (F)

Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.

Mohammad Abdollahi (M)

Toxicology and Diseases Group, Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), and Department of Toxicology and Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Ehsan Arefian (E)

Molecular Virology Lab, Department of Microbiology, School of Biology, College of Science, University of Tehran, Tehran, Iran.

Reza Lotfizadeh (R)

Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran.

Houri Sepehri (H)

Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran.

Mahdi Moridi Farimani (M)

Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, Iran.

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