New inhibitor of the TAp73 interaction with MDM2 and mutant p53
with promising antitumor activity against neuroblastoma

J 2019

New inhibitor of the TAp73 interaction with MDM2 and mutant p53 with promising antitumor activity against neuroblastoma

GOMES, Sara; Liliana Sofia Gomes RAIMUNDO; Joana SOARES; Joana B. LOUREIRO; Mariana LEAO et. al.

Základní údaje

Originální název

New inhibitor of the TAp73 interaction with MDM2 and mutant p53 with promising antitumor activity against neuroblastoma

Autoři

Vydání

Cancer Letters, County Clare, ELSEVIER IRELAND LTD, 2019, 0304-3835

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Full Text

Impakt faktor

Impact factor: 7.360

Kód RIV

RIV/00216224:14310/19:00109297

Organizační jednotka

Přírodovědecká fakulta

DOI

https://doi.org/10.1016/j.canlet.2019.01.014

UT WoS

000458940700009

EID Scopus

2-s2.0-85060350984

Klíčová slova anglicky

p73; Carbaldehydic xanthone; Anticancer therapy

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 17. 3. 2020 12:06, Mgr. Marie Novosadová Šípková, DiS.

Anotace

V originále

TAp73 is a key tumor suppressor protein, regulating the transcription of unique and shared p53 target genes with crucial roles in tumorigenesis and therapeutic response. As such, in tumors with impaired p53 signaling, like neuroblastoma, TAp73 activation represents an encouraging strategy, alternative to p53 activation, to suppress tumor growth and chemoresistance. In this work, we report a new TAp73-activating agent, the 1-carbaldehyde-3,4-dimethoxyxanthone (LEM2), with potent antitumor activity. Notably, LEM2 was able to release TAp73 from its interaction with both MDM2 and mutant p53, enhancing TAp73 transcriptional activity, cell cycle arrest, and apoptosis in p53-null and mutant p53-expressing tumor cells. Importantly, LEM2 displayed potent antitumor activity against patient-derived neuroblastoma cells, consistent with an activation of the TAp73 pathway. Additionally, potent synergistic effects were obtained for the combination of LEM2 with doxorubicin and cisplatin in patient-derived neuroblastoma cells. Collectively, besides its relevant contribution to the advance of TAp73 pharmacology, LEM2 may pave the way to improved therapeutic alternatives against neuroblastoma.

Návaznosti

MUNI/A/0824/2017, interní kód MU

Název: Podpora výzkumné činnosti studentů molekulární biologie a genetiky 6 (Akronym: MolBiolGen)

Investor: Masarykova univerzita, Podpora výzkumné činnosti studentů molekulární biologie a genetiky 6, DO R. 2020_Kategorie A - Specifický výzkum - Studentské výzkumné projekty

Citovat

GOMES, Sara; Liliana Sofia Gomes RAIMUNDO; Joana SOARES; Joana B. LOUREIRO; Mariana LEAO; Helena Isabel NOGUEIRA RAMOS ROCHA; Madalena N. MONTEIRO; Agostinho LEMOS; Joana MOREIRA; Madalena PINTO; Petr CHLAPEK; Renata VESELSKÁ; Emília SOUSA a Lucília SARAIVA. New inhibitor of the TAp73 interaction with MDM2 and mutant p53 with promising antitumor activity against neuroblastoma. Cancer Letters. County Clare: ELSEVIER IRELAND LTD, 2019, roč. 446, č. 4, s. 90-102. ISSN 0304-3835. Dostupné z: https://doi.org/10.1016/j.canlet.2019.01.014.

@article{1506137,
   author = {Gomes, Sara and Raimundo, Liliana Sofia Gomes and Soares, Joana and Loureiro, Joana B. and Leao, Mariana and Nogueira Ramos Rocha, Helena Isabel and Monteiro, Madalena N. and Lemos, Agostinho and Moreira, Joana and Pinto, Madalena and Chlapek, Petr and Veselská, Renata and Sousa, Emília and Saraiva, Lucília},
   article_location = {County Clare},
   article_number = {4},
   doi = {https://doi.org/10.1016/j.canlet.2019.01.014},
   keywords = {p73; Carbaldehydic xanthone; Anticancer therapy},
   language = {eng},
   issn = {0304-3835},
   journal = {Cancer Letters},
   title = {New inhibitor of the TAp73 interaction with MDM2 and mutant p53 with promising antitumor activity against neuroblastoma},
   url = {https://www.sciencedirect.com/science/article/pii/S0304383519300266},
   volume = {446},
   year = {2019}
}

TY  - JOUR
ID  - 1506137
AU  - Gomes, Sara - Raimundo, Liliana Sofia Gomes - Soares, Joana - Loureiro, Joana B. - Leao, Mariana - Nogueira Ramos Rocha, Helena Isabel - Monteiro, Madalena N. - Lemos, Agostinho - Moreira, Joana - Pinto, Madalena - Chlapek, Petr - Veselská, Renata - Sousa, Emília - Saraiva, Lucília
PY  - 2019
TI  - New inhibitor of the TAp73 interaction with MDM2 and mutant p53 with promising antitumor activity against neuroblastoma
JF  - Cancer Letters
VL  - 446
IS  - 4
SP  - 90-102
EP  - 90-102
PB  - ELSEVIER IRELAND LTD
SN  - 03043835
KW  - p73
KW  - Carbaldehydic xanthone
KW  - Anticancer therapy
UR  - https://www.sciencedirect.com/science/article/pii/S0304383519300266
L2  - https://www.sciencedirect.com/science/article/pii/S0304383519300266
N2  - TAp73 is a key tumor suppressor protein, regulating the transcription of unique and shared p53 target genes with crucial roles in tumorigenesis and therapeutic response. As such, in tumors with impaired p53 signaling, like neuroblastoma, TAp73 activation represents an encouraging strategy, alternative to p53 activation, to suppress tumor growth and chemoresistance. In this work, we report a new TAp73-activating agent, the 1-carbaldehyde-3,4-dimethoxyxanthone (LEM2), with potent antitumor activity. Notably, LEM2 was able to release TAp73 from its interaction with both MDM2 and mutant p53, enhancing TAp73 transcriptional activity, cell cycle arrest, and apoptosis in p53-null and mutant p53-expressing tumor cells. Importantly, LEM2 displayed potent antitumor activity against patient-derived neuroblastoma cells, consistent with an activation of the TAp73 pathway. Additionally, potent synergistic effects were obtained for the combination of LEM2 with doxorubicin and cisplatin in patient-derived neuroblastoma cells. Collectively, besides its relevant contribution to the advance of TAp73 pharmacology, LEM2 may pave the way to improved therapeutic alternatives against neuroblastoma.
ER  -

GOMES, Sara; Liliana Sofia Gomes RAIMUNDO; Joana SOARES; Joana B. LOUREIRO; Mariana LEAO; Helena Isabel NOGUEIRA RAMOS ROCHA; Madalena N. MONTEIRO; Agostinho LEMOS; Joana MOREIRA; Madalena PINTO; Petr CHLAPEK; Renata VESELSKÁ; Emília SOUSA a Lucília SARAIVA. New inhibitor of the TAp73 interaction with MDM2 and mutant p53 with promising antitumor activity against neuroblastoma. \textit{Cancer Letters}. County Clare: ELSEVIER IRELAND LTD, 2019, roč.~446, č.~4, s.~90-102. ISSN~0304-3835. Dostupné z: https://doi.org/10.1016/j.canlet.2019.01.014.

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