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Original Articles
Parthenolide promotes apoptotic cell death and inhibits the migration and invasion of SW620 cells
Yu Chuan Liu, Se Lim Kim, Young Ran Park, Soo-Teik Lee, Sang Wook Kim
Intest Res 2017;15(2):174-181.   Published online April 27, 2017
DOI: https://doi.org/10.5217/ir.2017.15.2.174
AbstractAbstract PDFPubReaderePub
<b>Background/Aims</b><br/>

Parthenolide (PT), a principle component derived from feverfew (Tanacetum parthenium), is a promising anticancer agent and has been shown to promote apoptotic cell death in various cancer cells. In this study, we focused on its functional role in apoptosis, migration, and invasion of human colorectal cancer (CRC) cells.

Methods

SW620 cells were employed as representative human CRC cells. We performed the MTT assay and cell cycle analysis to measure apoptotic cell death. The wound healing, Transwell migration, and Matrigel invasion assays were performed to investigate the effect of PT on cell migration/invasion. Western blotting was used to establish the signaling pathway of apoptosis and cell migration/invasion.

Results

PT exerts antiproliferative effect and induces apoptotic cell death of SW620 cells. In addition, PT prevents cell migration and invasion in a dose-dependent manner. Moreover, PT markedly suppressed migration/invasion-related protein expression, including E-cadherin, β-catenin, vimentin, Snail, cyclooxygenase-2, matrix metalloproteinase-2 (MMP-2), and MMP-9 in SW620 cells. PT also inhibited the expression of antiapoptotic proteins (Bcl-2 and Bcl-xL) and activated apoptosis terminal factor (caspase-3) in a dose-dependent manner.

Conclusions

Our results suggest that PT is a potential novel therapeutic agent for aggressive CRC treatment.

Citations

Citations to this article as recorded by  
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    Fatemeh Mehdikhani, Homa Hajimehdipoor, Mojgan Tansaz, Marc Maresca, Sadegh Rajabi
    Biomolecules.2025; 15(2): 268.     CrossRef
  • Sesquiterpene lactones and cancer: new insight into antitumor and anti-inflammatory effects of parthenolide-derived Dimethylaminomicheliolide and Micheliolide
    Jian Li, Xin Li, Hongwei Liu
    Frontiers in Pharmacology.2025;[Epub]     CrossRef
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    Jian Chang, Geqiong Xiao
    Toxicology and Applied Pharmacology.2025; 497: 117268.     CrossRef
  • Novel formulation of parthenolide-loaded liposome coated with chitosan and evaluation of its potential anticancer effects in vitro
    Parisa Karimian Ensaf, Mohammad Taghi Goodarzi, Masoud Homayouni Tabrizi, Ali Neamati, Samira Sadat Hosseinyzadeh
    Molecular Biology Reports.2024;[Epub]     CrossRef
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    Frontiers in Pharmacology.2024;[Epub]     CrossRef
  • Exploring the Phytochemistry, Signaling Pathways, and Mechanisms of Action of Tanacetum parthenium (L.) Sch.Bip.: A Comprehensive Literature Review
    Ali Kashkooe, Atefeh Jalali, Mohammad M. Zarshenas, Azadeh Hamedi
    Biomedicines.2024; 12(10): 2297.     CrossRef
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    Ana R. Costa, Ana C. Duarte, Ana R. Costa-Brito, Isabel Gonçalves, Cecília R.A. Santos
    Life Sciences.2023; 315: 121363.     CrossRef
  • Parthenolide inhibits proliferation and invasion, promotes apoptosis, and reverts the cell–cell adhesion loss through downregulation of NF‐κB pathway TNF‐α‐activated in colorectal cancer cells
    Adriana S. Gehren, Waldemir F. de Souza, Annie C. M. Sousa‐Squiavinato, Diego A. A. Ramos, Bruno R. B. Pires, Eliana S. F. W. Abdelhay, Jose A. Morgado‐Diaz
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    Process Biochemistry.2023; 132: 297.     CrossRef
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    Soad L. Kabil, Hayam E. Rashed, Noura Mostafa Mohamed, Nisreen E. Elwany
    Life Sciences.2023; 331: 122037.     CrossRef
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    Sumeet Singh, Vinita Gouri, Mukesh Samant
    Medical Oncology.2023;[Epub]     CrossRef
  • Decoding Systems Biology of Inflammation Signatures in Cancer Pathogenesis: Pan-Cancer Insights from 12 Common Cancers
    Beste Turanli
    OMICS: A Journal of Integrative Biology.2023; 27(10): 483.     CrossRef
  • Parthenolide and Its Soluble Analogues: Multitasking Compounds with Antitumor Properties
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    Biomedicines.2022; 10(2): 514.     CrossRef
  • Parthenolide reverses the epithelial to mesenchymal transition process in breast cancer by targeting TGFbeta1: In vitro and in silico studies
    Hazera Binte Sufian, Julianna Maria Santos, Zeina S. Khan, Sobia Ahsan Halim, Ajmal Khan, Maliha Tabassum Munir, MD Khurshidul Zahid, Ahmed Al-Harrasi, Lauren S. Gollahon, Fazle Hussain, Shaikh Mizanoor Rahman
    Life Sciences.2022; 301: 120610.     CrossRef
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    Cancers.2021; 13(8): 1786.     CrossRef
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    Journal of Cellular Biochemistry.2019; 120(2): 1386.     CrossRef
  • Collateral Sensitivity of Parthenolide via NF-κB and HIF-α Inhibition and Epigenetic Changes in Drug-Resistant Cancer Cell Lines
    Mona Dawood, Edna Ooko, Thomas Efferth
    Frontiers in Pharmacology.2019;[Epub]     CrossRef
  • 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
    Intestinal Research.2019; 17(4): 527.     CrossRef
  • Redox Paradox: A Novel Approach to Therapeutics-Resistant Cancer
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    Antioxidants & Redox Signaling.2018; 29(13): 1237.     CrossRef
  • Parthenolide inhibits tumor-promoting effects of nicotine in lung cancer by inducing P53 - dependent apoptosis and inhibiting VEGF expression
    Wamidh H. Talib, Lina T. Al Kury
    Biomedicine & Pharmacotherapy.2018; 107: 1488.     CrossRef
  • Synergistic effects and mechanisms of impressic acid or acankoreanogein in combination with docetaxel on prostate cancer
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    RSC Advances.2018; 8(5): 2768.     CrossRef
  • The combined administration of parthenolide and ginsenoside CK in long circulation liposomes with targeted tLyp-1 ligand induce mitochondria-mediated lung cancer apoptosis
    Xin Jin, Jianping Zhou, Zhenhai Zhang, Huixia Lv
    Artificial Cells, Nanomedicine, and Biotechnology.2018; 46(sup3): 931.     CrossRef
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  • 28 Crossref
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Parthenolide Sensitizes Human Colorectal Cancer Cells to Tumor Necrosis Factor-related Apoptosis-inducing Ligand through Mitochondrial and Caspase Dependent Pathway
Kieu Thi Thu Trang, Se-Lim Kim, Sang-Bae Park, Seung-Young Seo, Chung-Hwan Choi, Jin-Kyoung Park, Jin-Chang Moon, Soo-Teik Lee, Sang-Wook Kim
Intest Res 2014;12(1):34-41.   Published online January 28, 2014
DOI: https://doi.org/10.5217/ir.2014.12.1.34
AbstractAbstract PDFPubReader
<b>Background/Aims</b><br/>

Combination therapy utilizing tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in conjunction with other anticancer agents, is a promising strategy to overcome TRAIL resistance in malignant cells. Recently, parthenolide (PT) has proved to be a promising anticancer agent, and several studies have explored its use in combination therapy. Here, we investigated the molecular mechanisms by which PT sensitizes colorectal cancer (CRC) cells to TRAIL-induced apoptosis.

Methods

HT-29 cells (TRAIL-resistant) were treated with PT and/or TRAIL for 24 hours. The inhibitory effect on proliferation was detected using the 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Annexin V staining, cell cycle analysis, and Hoechst 33258 staining were used to assess apoptotic cell death. Activation of an apoptotic pathway was confirmed by Western blot.

Results

Treatment with TRAIL alone inhibited the proliferation of HCT 116 cells in a dose-dependent manner, whereas proliferation was not affected in HT-29 cells. Combination PT and TRAIL treatment significantly inhibited cell growth and induced apoptosis of HT-29 cells. We observed that the synergistic effect was associated with misregulation of B-cell lymphoma 2 (Bcl-2) family members, release of cytochrome C to the cytosol, activation of caspases, and increased levels of p53.

Conclusion

Combination therapy using PT and TRAIL might offer an effetive strategy to overcome TRAIL resistance in certain CRC cells.

Citations

Citations to this article as recorded by  
  • Nanomagnetic Liposome-Encapsulated Parthenolide and Indocyanine Green for Targeting and Chemo-Photothermal Antitumor Therapy
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    Nanomedicine.2020; 15(9): 871.     CrossRef
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  • Down‐regulation of intracellular anti‐apoptotic proteins, particularly c‐FLIP by therapeutic agents; the novel view to overcome resistance to TRAIL
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    Gabriela Flores‐Lopez, Dafne Moreno‐Lorenzana, Manuel Ayala‐Sanchez, Socrates Aviles‐Vazquez, Hector Torres‐Martinez, Peter A. Crooks, Monica L. Guzman, Hector Mayani, Antonieta Chávez‐González
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    Se-Lim Kim, Seong Hun Kim, Young Ran Park, Yu-Chuan Liu, Eun-Mi Kim, Hwan-Jeong Jeong, Yo Na Kim, Seung Young Seo, In Hee Kim, Seung Ok Lee, Soo Teik Lee, Sang-Wook Kim
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  • Sesquiterpene lactones of Moquiniastrum polymorphum subsp. floccosum have antineoplastic effects in Walker-256 tumor-bearing rats
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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
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  • 8,865 View
  • 47 Download
  • 15 Web of Science
  • 11 Crossref
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