Abstract |
Chemo-resistance and metastasis are the most common causes of breast cancer recurrence and death. Thidiazuron (TDZ) is a plant growth regulator ( phytohormone) whose biological effects on humans and animals has not yet been determined. In this study, we investigated the anticancer activity of this phytohormone on the drug resistant- triple negative breast cancer cell line MDA-MB-231. Treatment of the breast cancer cells with TDZ (1-50 μmol/L) caused more stressful environment and induced a significant increase in active caspase-positive cells. In addition, TDZ treatment (5 and 10 μmol/L) significantly attenuated the migration and the invasiveness of these highly metastatic cancer cells. Mechanistically, TDZ reduces cancer progression and invasiveness by targeting miR-202-5p, which stimulates the expression of phosphatase and tensin homolog (PTEN), the tumor suppressor that downregulates the PI3K-Akt signaling pathway. Treatment with TDZ significantly upregulates miRNA-132, the suppressor of breast cancer proliferation, which is also implicated in dysregulation of the TEN-Akt-NFκB signaling pathway. Interestingly, our molecular docking analysis revealed a potential non-covalent interaction between TDZ and Akt, PTEN, and PI3K. These findings suggest that TDZ suppresses breast cancer metastasis by targeting miRNA-132, the miR-202-5p-PTEN axis, and the PI3K-Akt signaling pathway downstream.
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Authors | Hairul-Islam Mohamed Ibrahim, Mohammad Bani Ismail, Rebai Ben Ammar, Emad A Ahmed |
Journal | Biochemistry and cell biology = Biochimie et biologie cellulaire
(Biochem Cell Biol)
Vol. 99
Issue 3
Pg. 374-384
(06 2021)
ISSN: 1208-6002 [Electronic] Canada |
PMID | 33103467
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Biomarkers, Tumor
- MIRN132 microRNA, human
- MIRN202 microRNA, human
- MicroRNAs
- Phenylurea Compounds
- Thiadiazoles
- thidiazuron
- Proto-Oncogene Proteins c-akt
- PTEN Phosphohydrolase
- PTEN protein, human
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Topics |
- Apoptosis
- Biomarkers, Tumor
(genetics, metabolism)
- Breast Neoplasms
(drug therapy, genetics, metabolism, pathology)
- Cell Proliferation
- Female
- Gene Expression Regulation, Neoplastic
(drug effects)
- Humans
- MicroRNAs
(genetics)
- Neoplasm Invasiveness
- PTEN Phosphohydrolase
(genetics, metabolism)
- Phenylurea Compounds
(pharmacology)
- Phosphatidylinositol 3-Kinases
(genetics, metabolism)
- Proto-Oncogene Proteins c-akt
(genetics, metabolism)
- Thiadiazoles
(pharmacology)
- Tumor Cells, Cultured
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