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Apigenin Suppresses the IL-1β-Induced Expression of the Urokinase-Type Plasminogen Activator Receptor by Inhibiting MAPK-Mediated AP-1 and NF-κB Signaling in Human Bladder Cancer T24 Cells.
J Agric Food Chem. 2018 Jul 25; 66(29):7663-7673.JA

Abstract

The urokinase-type plasminogen activator receptor (uPAR), a glycoprotein localized on the cell surface with a glycosylphosphatidylinositol anchor, plays a crucial role in cell invasion, and the metastasis of several cancers, including bladder cancer, and its expression are significantly negatively correlated with patient survival rates. Apigenin, a naturally produced phytochemical compound found in fruits, vegetables, and plant leaves, has been shown to mediate a variety of cancer-metastasis-related molecules in various cancers. The effect of apigenin on uPAR expression is still unknown. In this study, we examined the effects of apigenin on IL-1β-induced uPAR expression and investigated its potential mechanisms. We discovered in this study that IL-1β could remarkably induce uPAR expression in bladder cancer T24 cells and that apigenin-inhibited IL-1β could induce uPAR expression concentration-dependently. Interestingly, NF-κB and AP-1 transcription factors were critically required for IL-1β-induced high uPAR expression. Apigenin suppressed the transcriptional activity of both AP-1 and NF-κB by inhibiting ERK1/2 and JNK signaling pathways. These results suggest that apigenin can exert anti-invasion effects by inhibiting uPAR expression via mediating (ERK1/2, JNK)/AP-1 and (ERK1/2, JNK)/NF-κB signaling pathways in human T24 cells. Our present study generated novel and valuable biological insight into anti-invasion through treatment with a small native compound.

Authors+Show Affiliations

Research Institute of Medical Sciences , Chonnam National University Medical School , Gwangju 501-190 , Republic of Korea. Department of Urology , New York University School of Medicine , New York , New York 10016 , United States.No affiliation info availableResearch Institute of Medical Sciences , Chonnam National University Medical School , Gwangju 501-190 , Republic of Korea.Research Institute of Medical Sciences , Chonnam National University Medical School , Gwangju 501-190 , Republic of Korea.Research Institute of Medical Sciences , Chonnam National University Medical School , Gwangju 501-190 , Republic of Korea.Research Institute of Medical Sciences , Chonnam National University Medical School , Gwangju 501-190 , Republic of Korea.No affiliation info availableGuangdong Provincial Key Laboratory of Biochip , Guangzhou , 510515 , Guangdong , China.Research Institute of Medical Sciences , Chonnam National University Medical School , Gwangju 501-190 , Republic of Korea.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29945448

Citation

Xia, Yong, et al. "Apigenin Suppresses the IL-1β-Induced Expression of the Urokinase-Type Plasminogen Activator Receptor By Inhibiting MAPK-Mediated AP-1 and NF-κB Signaling in Human Bladder Cancer T24 Cells." Journal of Agricultural and Food Chemistry, vol. 66, no. 29, 2018, pp. 7663-7673.
Xia Y, Yuan M, Li S, et al. Apigenin Suppresses the IL-1β-Induced Expression of the Urokinase-Type Plasminogen Activator Receptor by Inhibiting MAPK-Mediated AP-1 and NF-κB Signaling in Human Bladder Cancer T24 Cells. J Agric Food Chem. 2018;66(29):7663-7673.
Xia, Y., Yuan, M., Li, S., Thuan, U. T., Nguyen, T. T., Kang, T. W., Liao, W., Lian, S., & Jung, Y. D. (2018). Apigenin Suppresses the IL-1β-Induced Expression of the Urokinase-Type Plasminogen Activator Receptor by Inhibiting MAPK-Mediated AP-1 and NF-κB Signaling in Human Bladder Cancer T24 Cells. Journal of Agricultural and Food Chemistry, 66(29), 7663-7673. https://doi.org/10.1021/acs.jafc.8b02351
Xia Y, et al. Apigenin Suppresses the IL-1β-Induced Expression of the Urokinase-Type Plasminogen Activator Receptor By Inhibiting MAPK-Mediated AP-1 and NF-κB Signaling in Human Bladder Cancer T24 Cells. J Agric Food Chem. 2018 Jul 25;66(29):7663-7673. PubMed PMID: 29945448.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Apigenin Suppresses the IL-1β-Induced Expression of the Urokinase-Type Plasminogen Activator Receptor by Inhibiting MAPK-Mediated AP-1 and NF-κB Signaling in Human Bladder Cancer T24 Cells. AU - Xia,Yong, AU - Yuan,Miaomiao, AU - Li,Shinan, AU - Thuan,Ung Trong, AU - Nguyen,Thi Thinh, AU - Kang,Taek Won, AU - Liao,Wenzhen, AU - Lian,Sen, AU - Jung,Young Do, Y1 - 2018/07/09/ PY - 2018/6/28/pubmed PY - 2018/8/15/medline PY - 2018/6/28/entrez KW - AP-1 KW - MAPKs KW - NF-κB KW - apigenin KW - uPAR SP - 7663 EP - 7673 JF - Journal of agricultural and food chemistry JO - J Agric Food Chem VL - 66 IS - 29 N2 - The urokinase-type plasminogen activator receptor (uPAR), a glycoprotein localized on the cell surface with a glycosylphosphatidylinositol anchor, plays a crucial role in cell invasion, and the metastasis of several cancers, including bladder cancer, and its expression are significantly negatively correlated with patient survival rates. Apigenin, a naturally produced phytochemical compound found in fruits, vegetables, and plant leaves, has been shown to mediate a variety of cancer-metastasis-related molecules in various cancers. The effect of apigenin on uPAR expression is still unknown. In this study, we examined the effects of apigenin on IL-1β-induced uPAR expression and investigated its potential mechanisms. We discovered in this study that IL-1β could remarkably induce uPAR expression in bladder cancer T24 cells and that apigenin-inhibited IL-1β could induce uPAR expression concentration-dependently. Interestingly, NF-κB and AP-1 transcription factors were critically required for IL-1β-induced high uPAR expression. Apigenin suppressed the transcriptional activity of both AP-1 and NF-κB by inhibiting ERK1/2 and JNK signaling pathways. These results suggest that apigenin can exert anti-invasion effects by inhibiting uPAR expression via mediating (ERK1/2, JNK)/AP-1 and (ERK1/2, JNK)/NF-κB signaling pathways in human T24 cells. Our present study generated novel and valuable biological insight into anti-invasion through treatment with a small native compound. SN - 1520-5118 UR - https://www.unboundmedicine.com/medline/citation/29945448/Apigenin_Suppresses_the_IL_1β_Induced_Expression_of_the_Urokinase_Type_Plasminogen_Activator_Receptor_by_Inhibiting_MAPK_Mediated_AP_1_and_NF_κB_Signaling_in_Human_Bladder_Cancer_T24_Cells_ L2 - https://doi.org/10.1021/acs.jafc.8b02351 DB - PRIME DP - Unbound Medicine ER -