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- Title
Silibinin Inhibits TGF-ß-induced MMP-2 and MMP-9 Through Smad Signaling Pathway in Colorectal Cancer HT-29 Cells.
- Authors
Zare, Zahra; dizaj, Tina Nayerpour; Lohrasbi, Armaghan; Sheikhalishahi, Zakieh Sadat; Asadi, Amirhooman; Zakeri, Mana; Hosseinabadi, Fahimeh; Abazari, Omid; Abbasi, Mojtaba; Khanicheragh, Parisa
- Abstract
Background: Metastasis of cancer cells is the primary responsible for death in patients with colorectal cancer (CRC). Transforming growth factor-ß (TGF-ß)-induced matrix metalloproteinases (MMPs) are essential for the metastasis process. Silibinin is a natural compound extracted from the Silybum marianum that exhibits anti-neoplastic activity in cancer cell lines. In this study, we evaluated the effects of silibinin on MMP-2 and MMP-9 induced by TGF-ß in human HT-29 CRC cell line and the potential mechanism underlying the effects. Methods: The present in vitro study was done on the HT-29 cell line. The HT-29 cell line was cultured in RPMI1640 and exposed to TGF-ß (5 ng/ml) in the absence and presence of different concentrations of silibinin (10, 25, 50, and 100 µM). The effect of silibinin on HT-29 cell viability was measured with the MTT assay. A real-time polymerase chain reaction (Real-Time PCR) determined the relative mRNA expression of MMP-2 and MMP-9. Western blotting was employed to examine MMP-2 and MMP 9 protein expression and Smad2 phosphorylation. Results: Silibinin inhibits cell viability of HT-29 cell line at 24 hours in a dose-dependent manner. TGF-ß increased the mRNA and protein expression of MMP-2, MMP-9, and phosphorylated Smad2 compared to controls. Pharmacological inhibition with silibinin markedly blocked TGF-ß-induced MMP-2 and MMP-9 mRNA and protein expression and Smad2 phosphorylation. Conclusion: Silibinin decreased the cell viability of HT-29 cancer cells in a dose-dependent manner. Silibinin also inhibited TGF-ß-stimulated MMP-2 and MMP-9 expression in HT-29 cells, possibly mediated with the Smad2 signaling pathway.
- Subjects
SILIBININ; COLORECTAL cancer; CANCER cells; MATRIX metalloproteinases; POLYMERASE chain reaction
- Publication
Basic & Clinical Cancer Research, 2020, Vol 12, Issue 2, p81
- ISSN
2228-6527
- Publication type
Article