Parthenolide inhibits transforming growth factor β1-induced epithelial-mesenchymal transition in colorectal cancer cells
- Author:
Shi Mao ZHU
1
;
Yong Ran PARK
;
Seung Yong SEO
;
In Hee KIM
;
Soo Teik LEE
;
Sang Wook KIM
Author Information
- Publication Type:Original Article
- Keywords: Transforming growth factor beta 1; Epithelial-mesenchymal transition; Parthenolide; Colorectal neoplasms
- MeSH: Apoptosis; Blotting, Western; Cadherins; Cell Line; Cell Movement; Cell Proliferation; Cell Survival; Colorectal Neoplasms; Epithelial-Mesenchymal Transition; Flow Cytometry; Gastropoda; HT29 Cells; Humans; Microscopy, Phase-Contrast; Phosphotransferases; Snails; Transforming Growth Factors; Vimentin; Wounds and Injuries
- From:Intestinal Research 2019;17(4):527-536
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND/AIMS: Transforming growth factor-β1 (TGF-β1) induction of epithelial-mesenchymal transition (EMT) is one of the mechanisms by which colorectal cancer (CRC) cells acquire migratory and invasive capacities, and subsequently metastasize. Parthenolide (PT) expresses multiple anti-cancer and anti-inflammatory activities that inhibit nuclear factor κB by targeting the IκB kinase complex. In the present study, we aimed to investigate whether PT can inhibit TGF-β1-induced EMT in CRC cell lines.METHODS: HT-29 and SW480 cell lines were used in the experiment. Cell viability was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and sub-G1 analysis was measured by flow cytometry. The induction of EMT by TGF-β1 and inhibition of the process by PT was analyzed by phase contrast microscopy, wounding healing, cellular migration and invasion assays, and Western blotting.RESULTS: TGF-β1 inhibits HT-29 cell proliferation, but has no effect on SW480 cell proliferation; different concentrations of TGF-β1 did not induce apoptosis in HT-29 and SW480 cells. PT attenuates TGF-β1-induced elongated, fibroblast-like shape changing in cells. PT inhibits TGF-β1-induced cell migration and cell invasion. In addition, other EMT markers such as β-catenin, Vimentin, Snail, and Slug were suppressed by PT, while E-cadherin was increased by PT.CONCLUSIONS: Our findings show that PT inhibits TGF-β1-induced EMT by suppressing the expression of the mesenchymal protein and increasing expression of the epithelial protein. These findings suggest a novel approach for CRC treatment by suppression of TGF-β1-induced EMT.
