PMS1077 sensitizes TNF-α induced apoptosis in human prostate cancer cells by blocking NF-κB signaling pathway.
Our previous studies have demonstrated that PMS1077, a platelet-activating factor (PAF) antagonist, could induce apoptosis of Raji cells. However, the mechanism of action has not yet been determined. The nuclear transcription factor-kappa B (NF-κB) signaling pathway plays a critical role in tumor ce...
Guardado en:
| Autores principales: | , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2013
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/306cbc1f5ff04cafa91aa34ffbe4b048 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:306cbc1f5ff04cafa91aa34ffbe4b048 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:306cbc1f5ff04cafa91aa34ffbe4b0482021-11-18T07:49:53ZPMS1077 sensitizes TNF-α induced apoptosis in human prostate cancer cells by blocking NF-κB signaling pathway.1932-620310.1371/journal.pone.0061132https://doaj.org/article/306cbc1f5ff04cafa91aa34ffbe4b0482013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23593410/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Our previous studies have demonstrated that PMS1077, a platelet-activating factor (PAF) antagonist, could induce apoptosis of Raji cells. However, the mechanism of action has not yet been determined. The nuclear transcription factor-kappa B (NF-κB) signaling pathway plays a critical role in tumor cell survival, proliferation, invasion, metastasis, and angiogenesis, so we determined the effects of PMS1077 and its structural analogs on tumor necrosis factor-α (TNF-α) induced activation of NF-κB signaling. In this study, we found that PMS1077 inhibited TNF-α induced expression of the NF-κB regulated reporter gene in a dose dependent manner. Western blot assay indicated that PMS1077 suppressed the TNF-α induced inhibitor of κB-α (IκB-α) phosphorylation, IκB-α degradation, and p65 phosphorylation. PMS1077 consistently blocked TNF-α induced p65 nuclear translocation as demonstrated in the immunofluorescence assay used. Docking studies by molecular modeling predicted that PMS1077 might interact directly with the IκB kinase-β (IKK-β) subunit. These results suggested that PMS1077 might suppress the activation of NF-κB by targeting IKK-β involved in the NF-κB signaling pathway. Finally, we showed that PMS1077 sensitized cells to TNF-α induced apoptosis by suppressing the expression of NF-κB regulated anti-apoptotic genes. Our results reveal a novel function of PMS1077 on the NF-κB signaling pathway and imply that PMS1077 can be considered as an anti-tumor lead compound.Jie ShiJing ChenNawal SerradjiXiming XuHeng ZhouYinxing MaZhihong SunPeng JiangYuping DuJinbo YangChangzhi DongQin WangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 4, p e61132 (2013) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Jie Shi Jing Chen Nawal Serradji Ximing Xu Heng Zhou Yinxing Ma Zhihong Sun Peng Jiang Yuping Du Jinbo Yang Changzhi Dong Qin Wang PMS1077 sensitizes TNF-α induced apoptosis in human prostate cancer cells by blocking NF-κB signaling pathway. |
| description |
Our previous studies have demonstrated that PMS1077, a platelet-activating factor (PAF) antagonist, could induce apoptosis of Raji cells. However, the mechanism of action has not yet been determined. The nuclear transcription factor-kappa B (NF-κB) signaling pathway plays a critical role in tumor cell survival, proliferation, invasion, metastasis, and angiogenesis, so we determined the effects of PMS1077 and its structural analogs on tumor necrosis factor-α (TNF-α) induced activation of NF-κB signaling. In this study, we found that PMS1077 inhibited TNF-α induced expression of the NF-κB regulated reporter gene in a dose dependent manner. Western blot assay indicated that PMS1077 suppressed the TNF-α induced inhibitor of κB-α (IκB-α) phosphorylation, IκB-α degradation, and p65 phosphorylation. PMS1077 consistently blocked TNF-α induced p65 nuclear translocation as demonstrated in the immunofluorescence assay used. Docking studies by molecular modeling predicted that PMS1077 might interact directly with the IκB kinase-β (IKK-β) subunit. These results suggested that PMS1077 might suppress the activation of NF-κB by targeting IKK-β involved in the NF-κB signaling pathway. Finally, we showed that PMS1077 sensitized cells to TNF-α induced apoptosis by suppressing the expression of NF-κB regulated anti-apoptotic genes. Our results reveal a novel function of PMS1077 on the NF-κB signaling pathway and imply that PMS1077 can be considered as an anti-tumor lead compound. |
| format |
article |
| author |
Jie Shi Jing Chen Nawal Serradji Ximing Xu Heng Zhou Yinxing Ma Zhihong Sun Peng Jiang Yuping Du Jinbo Yang Changzhi Dong Qin Wang |
| author_facet |
Jie Shi Jing Chen Nawal Serradji Ximing Xu Heng Zhou Yinxing Ma Zhihong Sun Peng Jiang Yuping Du Jinbo Yang Changzhi Dong Qin Wang |
| author_sort |
Jie Shi |
| title |
PMS1077 sensitizes TNF-α induced apoptosis in human prostate cancer cells by blocking NF-κB signaling pathway. |
| title_short |
PMS1077 sensitizes TNF-α induced apoptosis in human prostate cancer cells by blocking NF-κB signaling pathway. |
| title_full |
PMS1077 sensitizes TNF-α induced apoptosis in human prostate cancer cells by blocking NF-κB signaling pathway. |
| title_fullStr |
PMS1077 sensitizes TNF-α induced apoptosis in human prostate cancer cells by blocking NF-κB signaling pathway. |
| title_full_unstemmed |
PMS1077 sensitizes TNF-α induced apoptosis in human prostate cancer cells by blocking NF-κB signaling pathway. |
| title_sort |
pms1077 sensitizes tnf-α induced apoptosis in human prostate cancer cells by blocking nf-κb signaling pathway. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/306cbc1f5ff04cafa91aa34ffbe4b048 |
| work_keys_str_mv |
AT jieshi pms1077sensitizestnfainducedapoptosisinhumanprostatecancercellsbyblockingnfkbsignalingpathway AT jingchen pms1077sensitizestnfainducedapoptosisinhumanprostatecancercellsbyblockingnfkbsignalingpathway AT nawalserradji pms1077sensitizestnfainducedapoptosisinhumanprostatecancercellsbyblockingnfkbsignalingpathway AT ximingxu pms1077sensitizestnfainducedapoptosisinhumanprostatecancercellsbyblockingnfkbsignalingpathway AT hengzhou pms1077sensitizestnfainducedapoptosisinhumanprostatecancercellsbyblockingnfkbsignalingpathway AT yinxingma pms1077sensitizestnfainducedapoptosisinhumanprostatecancercellsbyblockingnfkbsignalingpathway AT zhihongsun pms1077sensitizestnfainducedapoptosisinhumanprostatecancercellsbyblockingnfkbsignalingpathway AT pengjiang pms1077sensitizestnfainducedapoptosisinhumanprostatecancercellsbyblockingnfkbsignalingpathway AT yupingdu pms1077sensitizestnfainducedapoptosisinhumanprostatecancercellsbyblockingnfkbsignalingpathway AT jinboyang pms1077sensitizestnfainducedapoptosisinhumanprostatecancercellsbyblockingnfkbsignalingpathway AT changzhidong pms1077sensitizestnfainducedapoptosisinhumanprostatecancercellsbyblockingnfkbsignalingpathway AT qinwang pms1077sensitizestnfainducedapoptosisinhumanprostatecancercellsbyblockingnfkbsignalingpathway |
| _version_ |
1718422902731177984 |