(-)-Epigallocatechin-3-Gallate Prevents IL-1β-Induced uPAR Expression and Invasiveness via the Suppression of NF-κB and AP-1 in Human Bladder Cancer Cells
(-)-Epigallocatechin-3-O-gallate (EGCG), a primary green tea polyphenol, has powerful iron scavengers, belongs to the family of flavonoids with antioxidant properties, and can be used to prevent cancer. Urokinase-type plasminogen activator receptors (uPARs) are glycosylphosphatidylinositol (GPI)-anc...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/22/14008 |
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| author | Dhiraj Kumar Sah Pham Ngoc Khoi Shinan Li Archana Arjunan Jae-Uk Jeong Young Do Jung |
| author_facet | Dhiraj Kumar Sah Pham Ngoc Khoi Shinan Li Archana Arjunan Jae-Uk Jeong Young Do Jung |
| author_sort | Dhiraj Kumar Sah |
| collection | DOAJ |
| description | (-)-Epigallocatechin-3-O-gallate (EGCG), a primary green tea polyphenol, has powerful iron scavengers, belongs to the family of flavonoids with antioxidant properties, and can be used to prevent cancer. Urokinase-type plasminogen activator receptors (uPARs) are glycosylphosphatidylinositol (GPI)-anchored cell membrane receptors that have crucial roles in cell invasion and metastasis of several cancers including bladder cancer. The mechanism of action of EGCG on uPAR expression has not been reported clearly yet. In this study, we investigated the effect of EGCG on interleukin (IL)-1β-induced cell invasion and uPAR activity in T24 human bladder cancer cells. Interestingly, nuclear factor (NF)-κB and activator protein (AP)-1 transcription factors were critically required for IL-1β-induced high uPAR expression, and EGCG suppressed the transcriptional activity of both the ERK1/2 and JNK signaling pathways with the AP-1 subunit c-Jun. EGCG blocked the IL-1β-stimulated reactive oxygen species (ROS) production, in turn suppressing NF-κB signaling and anti-invasion effects by inhibiting uPAR expression. These results suggest that EGCG may exert at least part of its anticancer effect by controlling uPAR expression through the suppression of ERK1/2, JNK, AP-1, and NF-κB. |
| first_indexed | 2024-03-09T18:17:24Z |
| format | Article |
| id | doaj.art-1cfa82d3f047439d9ec675e67889fc38 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T18:17:24Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1cfa82d3f047439d9ec675e67889fc382023-11-24T08:37:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123221400810.3390/ijms232214008(-)-Epigallocatechin-3-Gallate Prevents IL-1β-Induced uPAR Expression and Invasiveness via the Suppression of NF-κB and AP-1 in Human Bladder Cancer CellsDhiraj Kumar Sah0Pham Ngoc Khoi1Shinan Li2Archana Arjunan3Jae-Uk Jeong4Young Do Jung5Department of Biochemistry, Chonnam National University Medical School, Hwasun 58128, Republic of KoreaFaculty of Basic Medical Sciences, Pham Ngoc Thach University of Medicine, Ho Chi Minh City 740500, VietnamDepartment of Biochemistry, Chonnam National University Medical School, Hwasun 58128, Republic of KoreaDepartment of Biochemistry, Chonnam National University Medical School, Hwasun 58128, Republic of KoreaDepartment of Radiation Oncology, Chonnam National University Medical School, Hwasun 58128, Republic of KoreaDepartment of Biochemistry, Chonnam National University Medical School, Hwasun 58128, Republic of Korea(-)-Epigallocatechin-3-O-gallate (EGCG), a primary green tea polyphenol, has powerful iron scavengers, belongs to the family of flavonoids with antioxidant properties, and can be used to prevent cancer. Urokinase-type plasminogen activator receptors (uPARs) are glycosylphosphatidylinositol (GPI)-anchored cell membrane receptors that have crucial roles in cell invasion and metastasis of several cancers including bladder cancer. The mechanism of action of EGCG on uPAR expression has not been reported clearly yet. In this study, we investigated the effect of EGCG on interleukin (IL)-1β-induced cell invasion and uPAR activity in T24 human bladder cancer cells. Interestingly, nuclear factor (NF)-κB and activator protein (AP)-1 transcription factors were critically required for IL-1β-induced high uPAR expression, and EGCG suppressed the transcriptional activity of both the ERK1/2 and JNK signaling pathways with the AP-1 subunit c-Jun. EGCG blocked the IL-1β-stimulated reactive oxygen species (ROS) production, in turn suppressing NF-κB signaling and anti-invasion effects by inhibiting uPAR expression. These results suggest that EGCG may exert at least part of its anticancer effect by controlling uPAR expression through the suppression of ERK1/2, JNK, AP-1, and NF-κB.https://www.mdpi.com/1422-0067/23/22/14008AP-1cell invasionEGCGIL-1βUrokinase-type plasminogen activator receptor (uPAR)NF-κB |
| spellingShingle | Dhiraj Kumar Sah Pham Ngoc Khoi Shinan Li Archana Arjunan Jae-Uk Jeong Young Do Jung (-)-Epigallocatechin-3-Gallate Prevents IL-1β-Induced uPAR Expression and Invasiveness via the Suppression of NF-κB and AP-1 in Human Bladder Cancer Cells International Journal of Molecular Sciences AP-1 cell invasion EGCG IL-1β Urokinase-type plasminogen activator receptor (uPAR) NF-κB |
| title | (-)-Epigallocatechin-3-Gallate Prevents IL-1β-Induced uPAR Expression and Invasiveness via the Suppression of NF-κB and AP-1 in Human Bladder Cancer Cells |
| title_full | (-)-Epigallocatechin-3-Gallate Prevents IL-1β-Induced uPAR Expression and Invasiveness via the Suppression of NF-κB and AP-1 in Human Bladder Cancer Cells |
| title_fullStr | (-)-Epigallocatechin-3-Gallate Prevents IL-1β-Induced uPAR Expression and Invasiveness via the Suppression of NF-κB and AP-1 in Human Bladder Cancer Cells |
| title_full_unstemmed | (-)-Epigallocatechin-3-Gallate Prevents IL-1β-Induced uPAR Expression and Invasiveness via the Suppression of NF-κB and AP-1 in Human Bladder Cancer Cells |
| title_short | (-)-Epigallocatechin-3-Gallate Prevents IL-1β-Induced uPAR Expression and Invasiveness via the Suppression of NF-κB and AP-1 in Human Bladder Cancer Cells |
| title_sort | epigallocatechin 3 gallate prevents il 1β induced upar expression and invasiveness via the suppression of nf κb and ap 1 in human bladder cancer cells |
| topic | AP-1 cell invasion EGCG IL-1β Urokinase-type plasminogen activator receptor (uPAR) NF-κB |
| url | https://www.mdpi.com/1422-0067/23/22/14008 |
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