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Colorectal neoplasia
Parthenolide inhibits transforming growth factor β1-induced epithelial-mesenchymal transition in colorectal cancer cells
Shi Mao Zhu, Yong Ran Park, Seung Yong Seo, In Hee Kim, Soo Teik Lee, Sang Wook Kim
Intest Res 2019;17(4):527-536.   Published online August 23, 2019
DOI: https://doi.org/10.5217/ir.2019.00031
AbstractAbstract PDFPubReaderePub
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.

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    Biomedicines.2025; 13(1): 133.     CrossRef
  • Sesquiterpene lactones and cancer: new insight into antitumor and anti-inflammatory effects of parthenolide-derived Dimethylaminomicheliolide and Micheliolide
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  • Aniline-containing derivatives of parthenolide: Synthesis and anti-chronic lymphocytic leukaemia activity
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    Chang Hoon Lee
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Balsalazide Potentiates Parthenolide-Mediated Inhibition of Nuclear Factor-κB Signaling in HCT116 Human Colorectal Cancer Cells
Hyun-Young Kim, Se-Lim Kim, Young-Ran Park, Yu-Chuan Liu, Seung Young Seo, Seong Hun Kim, In Hee Kim, Seung Ok Lee, Soo Teik Lee, Sang Wook Kim
Intest Res 2015;13(3):233-241.   Published online June 9, 2015
DOI: https://doi.org/10.5217/ir.2015.13.3.233
AbstractAbstract PDFPubReader
<b>Background/Aims</b><br/>

Balsalazide is an anti-inflammatory drug used in the treatment of inflammatory bowel disease. Balsalazide can reduce inflammatory responses via several mechanisms, including inhibition of nuclear factor-κB (NF-κB) activity. Parthenolide (PT) inhibits NF-κB and exerts promising anticancer effects by promoting apoptosis. The present investigated the antitumor effects of balsalazide, combined with PT, on NF-κB in a representative human colorectal carcinoma cell line, HCT116.

Methods

We counted cells and conducted annexin-V assays and cell cycle analysis to measure apoptotic cell death. Western blotting was used investigate the levels of proteins involved in apoptosis.

Results

PT and balsalazide produced synergistic anti-proliferative effects and induced apoptotic cell death. The combination of balsalazide and PT markedly suppressed nuclear translocation of the NF-κB p65 subunit and the phosphorylation of inhibitor of NF-κB. Moreover, PT and balsalazide dramatically enhanced NF-κB p65 phosphorylation. Apoptosis, through the mitochondrial pathway, was confirmed by detecting effects on Bcl-2 family members, cytochrome c release, and activation of caspase-3 and -8.

Conclusions

Combination treatment with PT and balsalazide may offer an effective strategy for the induction of apoptosis in HCT116 cells.

Citations

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Does Metformin Affect The Incidence of Colonic Polyps and Adenomas in Patients with Type 2 Diabetes Mellitus?
Youn Hee Cho, Bong Min Ko, Shin Hee Kim, Yu Sik Myung, Jong Hyo Choi, Jae Pil Han, Su Jin Hong, Seong Ran Jeon, Hyun Gun Kim, Jin Oh Kim, Moon Sung Lee
Intest Res 2014;12(2):139-145.   Published online April 29, 2014
DOI: https://doi.org/10.5217/ir.2014.12.2.139
AbstractAbstract PDFPubReader
<b>Background/Aims</b><br/>

Colorectal cancer (CRC) develops from colonic adenomas. Type 2 diabetes mellitus (DM) is associated with a higher risk of CRC and metformin decreases CRC risk. However, it is not certain if metformin affects the development of colorectal polyps and adenomas. This study aimed to elucidate if metforminaffects the incidence of colonic polyps and adenomas in patients with type 2 DM.

Methods

Of 12,186 patients with type 2 DM, 3,775 underwent colonoscopy between May 2001 and March 2013. This study enrolled 3,105 of these patients, and divided them in two groups: 912 patients with metformin use and 2,193 patients without metformin use. Patient clinical characteristics, polyp and adenoma detection rate in the two groups were analyzed retrospectively.

Results

The Colorectal polyp detection rate was lower in the metformin group than in the non-meformin group (39.4% vs. 62.4%, P<0.01). Colorectal adenoma detection rate was significantly lower in the metformin group than in the non-metformin group (15.2% vs. 20.5%, P<0.01). Fewer advanced adenomas were detected in the metformin group than in the non-metformin group (12.2% vs. 22%, P<0.01). Multivariate analysis identified age, sex, Body mass index and metformin use as factors associated with polyp incidence, whereas only metforminwas independently associated with decreased adenoma incidence (Odd ratio=0.738, 95% CI=0.554-0.983, P=0.03).

Conclusions

In patients with type 2 DM, metformin reduced the incidence of adenomas that may transform into CRC. Therefore, metformin may be useful for the prevention of CRC in patients with type 2 DM.

Citations

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Synergistic Effect of Parthenolide in Combination with 5-Fluorouracil in SW480 Cells
Se-Lim Kim, Thu Trang Thi Kieu , Byung Jun Jeon, Seong Hun Kim, In Hee Kim, Seung Ok Lee, Soo Teik Lee, Sang Wook Kim
Intest Res 2012;10(4):357-364.   Published online October 31, 2012
DOI: https://doi.org/10.5217/ir.2012.10.4.357
AbstractAbstract PDF
Background/Aims
Parthenolide (PT) is responsible for the bioactivities of Feverfew. Besides its potent anti-inflammatory effect, this compound has recently been reported to induce apoptosis in cancer cells. Unfortunately, many of the therapies that use 5-fluorouracil (5-FU) alone or in combination with other agents are likely to become ineffective due to drug resistance. In the present study, we investigate the antitumor effect of PT combined with 5-FU on colorectal cancer cells. Methods: SW480 cell was employed as a representative of human colorectal carcinoma (CRC) cells. We performed MTT, annexin-V assay, and Hoechst 33258 staining to measure the synergistic effect. Western blotting was used to demonstrate apoptotic pathway. Results: Our result demonstrated that PT inhibited the viability of colorectal cancer cells and had synergistic anti-proliferation in combination with 5-FU. After combined treatment of 5-FU and PT, enhanced apoptotic cell death is observed using annexin-V FITC assay and it was revealed by the condensed chromatin and fragmented DNA. Compared with 5-FU or PT alone, the apoptosis of colorectal cancer cells treated with PT and 5-FU enhanced the activation of caspase-8, caspase-3. Conclusions: Combined treatment with PT may offer an efficacious strategy to overcome 5-FU resistance in certain CRC cells. (Intest Res 2012;10:357-364)

Citations

Citations to this article as recorded by  
  • Balsalazide Potentiates Parthenolide-Mediated Inhibition of Nuclear Factor-κB Signaling in HCT116 Human Colorectal Cancer Cells
    Hyun-Young Kim, Se-Lim Kim, Young-Ran Park, Yu-Chuan Liu, Seung Young Seo, Seong Hun Kim, In Hee Kim, Seung Ok Lee, Soo Teik Lee, Sang Wook Kim
    Intestinal Research.2015; 13(3): 233.     CrossRef
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