A new synthetic protein, TAT-RH, inhibits tumor growth through the regulation of NFκB activity
Background Based on its role in angiogenesis and apoptosis, the inhibition of NFκB activity is considered an effective treatment for cancer, hampered by the lack of selective and safe inhibitors. We recently demonstrated that the RH domain of GRK5 (GRK5-RH) inhibits NFκB, thus we evaluated its effects on cancer growth. Methods The role of GRK5-RH on tumor growth was assessed in a human cancer cell line (KAT-4). RH overexpression was induced by adenovirus mediated gene transfer; alternatively we administered a synthetic protein reproducing the RH domain of GRK5 (TAT-RH), actively transported into the cells. Results In vitro, adenovirus mediated GRK5-RH overexpression (AdGRK5-NT) in human tumor cells (KAT-4) induces IκB accumulation and inhibits NFκB transcriptional activity leading to apoptotic events. In BALB/c nude mice harboring KAT-4 induced neoplasias, intra-tumor delivery of AdGRK5-NT reduces in a dose-dependent fashion tumor growth, with the highest doses completely inhibiting it. This phenomenon is paralleled by a decrease of NFκB activity, an increase of IκB levels and apoptotic events. To move towards a pharmacological setup, we synthesized the TAT-RH protein. In cultured KAT-4 cells, different dosages of TAT-RH reduced cell survival and increased apoptosis. In BALB/c mice, the anti-proliferative effects of TAT-RH appear to be dose-dependent and highest dose completely inhibits tumor growth. Conclusion Our data suggest that GRK5-RH inhibition of NFκB is a novel and effective anti-tumoral strategy and TAT-RH could be an useful tool in the fighting of cancer..
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2009 |
|---|---|
| Erschienen: |
2009 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
|---|---|
| Enthalten in: |
Molecular cancer - 8(2009), 1 vom: 09. Nov. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Sorriento, Daniela [VerfasserIn] |
|---|
| Links: |
Volltext [lizenzpflichtig] |
|---|
| Themen: |
293N3S Cell |
|---|
| Anmerkungen: |
© Sorriento et al; licensee BioMed Central Ltd. 2009. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( |
|---|
| doi: |
10.1186/1476-4598-8-97 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
OLC2098712936 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | OLC2098712936 | ||
| 003 | DE-627 | ||
| 005 | 20230401184242.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230401s2009 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1186/1476-4598-8-97 |2 doi | |
| 035 | |a (DE-627)OLC2098712936 | ||
| 035 | |a (DE-He213)1476-4598-8-97-e | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 082 | 0 | 4 | |a 610 |a 570 |q VZ |
| 100 | 1 | |a Sorriento, Daniela |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a A new synthetic protein, TAT-RH, inhibits tumor growth through the regulation of NFκB activity |
| 264 | 1 | |c 2009 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a © Sorriento et al; licensee BioMed Central Ltd. 2009. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( | ||
| 520 | |a Background Based on its role in angiogenesis and apoptosis, the inhibition of NFκB activity is considered an effective treatment for cancer, hampered by the lack of selective and safe inhibitors. We recently demonstrated that the RH domain of GRK5 (GRK5-RH) inhibits NFκB, thus we evaluated its effects on cancer growth. Methods The role of GRK5-RH on tumor growth was assessed in a human cancer cell line (KAT-4). RH overexpression was induced by adenovirus mediated gene transfer; alternatively we administered a synthetic protein reproducing the RH domain of GRK5 (TAT-RH), actively transported into the cells. Results In vitro, adenovirus mediated GRK5-RH overexpression (AdGRK5-NT) in human tumor cells (KAT-4) induces IκB accumulation and inhibits NFκB transcriptional activity leading to apoptotic events. In BALB/c nude mice harboring KAT-4 induced neoplasias, intra-tumor delivery of AdGRK5-NT reduces in a dose-dependent fashion tumor growth, with the highest doses completely inhibiting it. This phenomenon is paralleled by a decrease of NFκB activity, an increase of IκB levels and apoptotic events. To move towards a pharmacological setup, we synthesized the TAT-RH protein. In cultured KAT-4 cells, different dosages of TAT-RH reduced cell survival and increased apoptosis. In BALB/c mice, the anti-proliferative effects of TAT-RH appear to be dose-dependent and highest dose completely inhibits tumor growth. Conclusion Our data suggest that GRK5-RH inhibition of NFκB is a novel and effective anti-tumoral strategy and TAT-RH could be an useful tool in the fighting of cancer. | ||
| 650 | 4 | |a Electrophoretic Mobility Shift Assay | |
| 650 | 4 | |a Green Fluorescen Protein Fluorescence | |
| 650 | 4 | |a 293N3S Cell | |
| 650 | 4 | |a Nude Mouse Tumor | |
| 650 | 4 | |a SYBR Green Real Time Polymerase Chain Reaction | |
| 700 | 1 | |a Campanile, Alfonso |4 aut | |
| 700 | 1 | |a Santulli, Gaetano |4 aut | |
| 700 | 1 | |a Leggiero, Eleonora |4 aut | |
| 700 | 1 | |a Pastore, Lucio |4 aut | |
| 700 | 1 | |a Trimarco, Bruno |4 aut | |
| 700 | 1 | |a Iaccarino, Guido |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Molecular cancer |d BioMed Central, 2002 |g 8(2009), 1 vom: 09. Nov. |h Online-Ressource |w (DE-627)355987619 |w (DE-600)2091373-4 |w (DE-576)107015234 |x 1476-4598 |7 nnns |
| 773 | 1 | 8 | |g volume:8 |g year:2009 |g number:1 |g day:09 |g month:11 |
| 856 | 4 | 0 | |u https://dx.doi.org/10.1186/1476-4598-8-97 |z lizenzpflichtig |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a SYSFLAG_A | ||
| 912 | |a GBV_OLC | ||
| 912 | |a GBV_ILN_20 | ||
| 912 | |a GBV_ILN_22 | ||
| 912 | |a GBV_ILN_23 | ||
| 912 | |a GBV_ILN_24 | ||
| 912 | |a GBV_ILN_31 | ||
| 912 | |a GBV_ILN_40 | ||
| 912 | |a GBV_ILN_60 | ||
| 912 | |a GBV_ILN_62 | ||
| 912 | |a GBV_ILN_63 | ||
| 912 | |a GBV_ILN_65 | ||
| 912 | |a GBV_ILN_69 | ||
| 912 | |a GBV_ILN_70 | ||
| 912 | |a GBV_ILN_73 | ||
| 912 | |a GBV_ILN_74 | ||
| 912 | |a GBV_ILN_95 | ||
| 912 | |a GBV_ILN_105 | ||
| 912 | |a GBV_ILN_110 | ||
| 912 | |a GBV_ILN_151 | ||
| 912 | |a GBV_ILN_161 | ||
| 912 | |a GBV_ILN_170 | ||
| 912 | |a GBV_ILN_206 | ||
| 912 | |a GBV_ILN_213 | ||
| 912 | |a GBV_ILN_230 | ||
| 912 | |a GBV_ILN_285 | ||
| 912 | |a GBV_ILN_293 | ||
| 912 | |a GBV_ILN_602 | ||
| 912 | |a GBV_ILN_702 | ||
| 912 | |a GBV_ILN_2001 | ||
| 912 | |a GBV_ILN_2003 | ||
| 912 | |a GBV_ILN_2005 | ||
| 912 | |a GBV_ILN_2006 | ||
| 912 | |a GBV_ILN_2007 | ||
| 912 | |a GBV_ILN_2008 | ||
| 912 | |a GBV_ILN_2009 | ||
| 912 | |a GBV_ILN_2010 | ||
| 912 | |a GBV_ILN_2011 | ||
| 912 | |a GBV_ILN_2014 | ||
| 912 | |a GBV_ILN_2015 | ||
| 912 | |a GBV_ILN_2020 | ||
| 912 | |a GBV_ILN_2021 | ||
| 912 | |a GBV_ILN_2025 | ||
| 912 | |a GBV_ILN_2031 | ||
| 912 | |a GBV_ILN_2038 | ||
| 912 | |a GBV_ILN_2044 | ||
| 912 | |a GBV_ILN_2048 | ||
| 912 | |a GBV_ILN_2055 | ||
| 912 | |a GBV_ILN_2056 | ||
| 912 | |a GBV_ILN_2057 | ||
| 912 | |a GBV_ILN_2061 | ||
| 912 | |a GBV_ILN_2111 | ||
| 912 | |a GBV_ILN_2113 | ||
| 912 | |a GBV_ILN_2134 | ||
| 912 | |a GBV_ILN_2136 | ||
| 912 | |a GBV_ILN_2190 | ||
| 912 | |a GBV_ILN_2433 | ||
| 912 | |a GBV_ILN_2446 | ||
| 912 | |a GBV_ILN_4012 | ||
| 912 | |a GBV_ILN_4037 | ||
| 912 | |a GBV_ILN_4112 | ||
| 912 | |a GBV_ILN_4125 | ||
| 912 | |a GBV_ILN_4126 | ||
| 912 | |a GBV_ILN_4249 | ||
| 912 | |a GBV_ILN_4305 | ||
| 912 | |a GBV_ILN_4306 | ||
| 912 | |a GBV_ILN_4307 | ||
| 912 | |a GBV_ILN_4313 | ||
| 912 | |a GBV_ILN_4322 | ||
| 912 | |a GBV_ILN_4323 | ||
| 912 | |a GBV_ILN_4324 | ||
| 912 | |a GBV_ILN_4325 | ||
| 912 | |a GBV_ILN_4338 | ||
| 912 | |a GBV_ILN_4367 | ||
| 912 | |a GBV_ILN_4700 | ||
| 951 | |a AR | ||
| 952 | |d 8 |j 2009 |e 1 |b 09 |c 11 | ||